[extropy-chat] Re:Resuscitation: and ArmchairCryonicists-hypothermic liferaft

Wed Dec 15 21:25:46 UTC 2004

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. :-)
  ----- Original Message ----- 
  From: Extropian Agroforestry Ventures Inc. 
  To: ExI chat list 
  Sent: Wednesday, December 15, 2004 7:56 AM
  Subject: Re: [extropy-chat] Re:Resuscitation: and ArmchairCryonicists-hypothermic liferaft

        United States Patent Application 20040097534  
        Kind Code  A1  
        Choi, Byung-Kil ;   et al.  May 20, 2004  

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  Composition for the protection and regeneration of nerve cells containing berberine derivatives 

  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.

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  [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. 

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  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)

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