Diazepam chemical structure
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Valium

Diazepam, market under brand names of: Valium, Seduxen; and in Europe Apozepam, Diapam, is a 1,4-benzodiazepine derivative, which possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Diazepam is used to treat anxiety and tension, and is the most effective benzodiazepine for treating muscle spasms. It is also used as a sedative premedication for various medical procedures, and to treat alcohol and opiate withdrawal symptoms. Occasionally, diazepam is used by military and paramilitary snipers to relax muscles and slow breathing for increased firing accuracy. Diazepam is a Schedule IV drug under the Convention on Psychotropic Substances. more...

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Diazepam is one of the 'standard benzodiazepines' most often used in clinics and for outpatients. It is enrolled in the WHO List of 'Essential Drugs'.

When introduced in 1963, it was the best of the new alternatives to barbiturates, drugs that could be deadly with an overdose. Diazepam (like the other benzodiazepines) did not have this danger, nor immediately obvious side effects, and became in widespread use to treat chronic anxiety. Diazepam was America's top-selling drug from 1969 to 1982, with peak sales in 1978 of 2.3 billion pills ($US600 million in sales).

However, it is now recognised that the drug is not as harmless as was first assumed. In the autumn of 1973, a report aired on the television show 60 Minutes attesting to the drug's addictiveness. This can occur in as little as four weeks. Following controversial and often polemic discussion prescriptions declined by nearly half in the 1980's and 1990's. Surprisingly, psychiatrists and neurologists have recently discovered new therapeutic fields for this 'old' drug diazepam (e.g. adjunctive treatment of extrapyramidal disorders, some forms of anxiety in children, and adjunctive treatment of spastic paresis); a process still ongoing.

Mode of action

In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. It binds in to specific benzodiazepine receptors, which are part of the GABA-receptors. When diazepam binds to this receptor, it causes an increase in the inhibitory effects of GABA. It is redistributed into tissues and fat deposits, and there is an adaptation of benzodiazepine receptors. In humans, tolerance to the sedative effects may develop within weeks, but tolerance to the anxiolytic efficiacy usually does not develop. Lorazepam, clonazepam and alprazolam show stronger anxiolytic effects compared to diazepam, but the former 3 drugs carry a particular high risk of abuse, misuse and psychological dependence.

Pharmacokinetics

Diazepam can be administered orally, intravenously or intramuscularly, or as a suppository. When taken orally, diazepam is rapidly absorbed and shows a fast onset of action. Absorption is much slower and more erratic when diazepam is given as an intramuscular injection. Diazepam is highly lipid-soluble and therefore crosses the blood-brain barrier easily. Diazepam is metabolised in the liver and it has a biphasic half-life. The half-life (t1/2α) is 20-100 hours, and its main active metabolite, desmethyldiazepam, has a half-life of 2-5 days. Diazepam's other active metabolites include, among others, temazepam and oxazepam. Diazepam and its metabolites are excreted into the urine.

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How umbilical cord stem cells are helping life imitate myth
From Townsend Letter for Doctors and Patients, 12/1/05 by Anthony G. Payne

We've all heard the expression "life imitates art." And it does, sometimes. In science, it could be said that progress sometimes imitates myth, or better yet, turns mythic feats into reality. And this is indeed what has emerged in terms of the response of many infants, children and adults with various eye, circulatory and especially, neurologic diseases and conditions, to treatment with human umbilical cord stem cells.

[ILLUSTRATION OMITTED]

Case-in-point: Last year the world was riveted by the announcement by South Korean scientists at Chosun University concerning how they had gotten Hwang Mi-Soon, a woman who'd been paralyzed for 19 years, out of her wheelchair and onto her feet 3 weeks after implanting human umbilical cord stem cells (hUCSC) into her spinal cord.

Interestingly, just three months prior to the Chosun University announcement, we at Steenblock Research Institute had wound down our analysis of a six month (March-August 2004) pilot study down in Mexico involving 8 children with cerebral palsy who'd received single injections of 1.5 million hUCSCs (subtype CD34+/133). In this study, treating physician Fernando Ramirez (Spinal Cord Regeneration Center, Tijuana, Mexico) administered the hUCSCs in a single subcutaneous injection near each child's umbilicus (navel). No immunosuppressant drugs were given and none of the children experienced any negative side effects or reactions to the treatment. Some children did experience unusual sleepiness following the injection, but this dissipated quickly.

Most of these children showed decreased spasticity and various kinds and degrees of motor skill and cognitive improvement following treatment. Analysis of specially designed questionnaires completed at regular intervals (pre- and post-) by parents and caregivers demonstrated statistically significant improvements in such areas of function as muscle tone, leg movement, hip movement, thinking and understanding. These assessments, while admittedly subjective, did receive additional support in the form of pre- and post-treatment video logs, as well as the results of standardized testing done by physical therapists and submitted by parents.

Most compelling was the fact that a 4 year-old little boy, Adam Susser, experienced a resolution of cortical blindness during the fourth month following his treatment. Adam's eyes worked perfectly, but the optic nerves that conducted the signals from his retinas to the visual centers of his brain were atrophied; so much so that leading ophthalmologists in his home state of Florida had predicted that he would never see. Readers interested in seeing a Sinclair Broadcast Group news segment on Adam's hUCSC treatment and response will find it on www.stemcelltherapies.org/resources.htm (Scroll down to item #12-"Watch a Stem Cell Video" and click this particular link).

SRI has documented similar improvements in many other children with CP (who were not part of the pilot study), as well as children and adults with traumatic brain injury, various eyes conditions including macular degeneration and diabetic retinopathy, early stage progressive and secondary progressive Multiple Sclerosis, early stage Lou Gehrig's disease, and recent stroke.

Here are but a sampling of the many case histories on file at SRI:

A. B. 74: stroke, glaucoma -- AB was legally blind in his left eye due to macular degeneration, complications of a stroke, and glaucoma. The vision in his affected eye tested out at 500/20. His eye was swollen and "blood red" at the time of treatment with pure umbilical cord stem cells which he received during January 2003. AB's vision steadily improved and was subsequently found to be 50/20 by his ophthalmologists at Massachusetts General Hospital. Due to this very positive response, Mr. B elected to have a second stem cell treatment during August 2003. About 3 weeks following his second treatment, Mr. B. reported that while little new improvement had taken place in his bad eye, he had begun to regain some use of a previously (stroke-caused) paralyzed left arm.

K.W.: Traumatic Brain Injury -- KW has a history of epileptic seizures, sleep disturbances and motor skill deficits. About one month following stem cell therapy (May 2003), his parents reported that he "hasn't had any more of those seizure-things since I last wrote you." KW's formerly lackluster appetite became quite robust, and he went from sleeping briefly at night to a more normal pattern for his age. KW, whose motor skills were far below normal, experienced slight increases in mobility, began kicking faster, rolling about more, expressed more curiosity about the world around him, and evinced improvements in his ability to memorize and recall information.

R.D.: Diabetes, Type I -- RD, a nurse whose diabetes had caused pronounced neuropathy and retinopathy, received an infusion of umbilical cord stem cells during 2003. The treatment did not alter her diabetic condition, but did reverse the neuropathy and restored her vision appreciably. For one thing, prior to stem cell therapy she had consistently failed the vision test portion of the California state driver's license examination. Eight months after umbilical cord stem cell therapy she passed the vision exam and received her license! RD noted this in a report to SRI: "As I am approaching the two year anniversary of receiving stem cells, I know that the distortions in my vision are less and I no longer have spots in my vision. Most recently, I have been able to read my writing and the computer screen without removing my long-distance glasses. I see most clearly on cloudy days as the glare of the sun is disturbing. I often see things that fully sighted people miss, perhaps due to the intentionality with which I visualize."

Alyssa Bavaro: Alyssa Bavaro, age 7, is a young girl with cerebral palsy who, like virtually all the children tracked by SRI, had been through the gamut of conventional therapies and healthcare measures for her condition. Her mother, Kelly, a "fighter" whose instincts for ferreting out the best for her daughter were honed by wrestling daily with doctors and therapists in New York City, had done her homework on hUCSCs by the time she approached SRI concerning how to hook up with Dr. Ramirez in Mexico. We at SRI provided Kelly with information to fill in the gaps in her self-education, and helped her get her daughter lined up to go to Mexico for treatment during April 2005.

Alyssa was treated on April 27th and almost immediately began to display a voracious appetite. This was of no concern to Mom, because Alyssa was very underweight and short for her age. During the next 4 months Alyssa gained 4 inches in height and about 15 pounds or so in added weight. Most exciting of all, longstanding spasticity in her body began to lessen.

Alyssa's story attracted the interest of ABC's flagship station in New York City, channel 7, and ultimately became a news segment featuring reporter Kimberly Richardson that aired in prime time during late May (2005).

Jordan Logan: Jordan Logan has a terminal, incurable neurologic disease called Metachromatic Leukodystrophy or MLD. MLD is a white matter wasting condition caused by a genetic defect in which a crucial enzyme called arylsulfatase A (ARS-A) is missing or poorly produced in the central nervous system. This is a progressive genetic disorder for which no treatment except supportive (palliative) exists. Children with advanced MDL such as Jordan typically die by age 5. Jordan is 4 years old.

During June 2005 Jordan had a treatment with 1.5 million human umbilical cord stem cells at Rio Valley Medical Clinic in Matamoras, Mexico (Frank Morales, MD, Medical Director). At the time she was limp as a rag doll, cortically blind and on 3 frequently dosed anti-seizure drugs and tranquilizers such as Valium. Within 2 months of her treatment, Jordan was moving her arms and legs, tracking objects with her eyes, and was using far less medication (One was discontinued by her doctors). Improvement in advanced MLD patients is considered a virtual impossibility by most informed experts in the field including leading neurologists at the NIH.

And in a historic first, on October 6th Jordan Logan received 1.5 million human umbilical cord stem cells into which the gene for ARS-A has been inserted ("transvected" in scientific parlance). Scientists in the East coast medical school-affiliated, FDA approved lab where these cells were processed, verified that they were producing and expressing the ARS-A enzyme during lab testing done prior to Jordan's treatment.

This step into biomedicine's "undiscovered country," began with a feasibility dialog between the author and the lab that produced the transvected hUCSCs. Dr. Morales' group and the medical school lab took this suggestion and ran with it.

The transvected hUCSC were administered by an associate of Frank Morales, MD, with Steenblock Research Institute providing technical support and data collection and analysis services to Morales' clinic. It should be noted that Dr. Morales donated his services and time (and that of his staff) to treat Jordan.

In addition, a good-hearted businessman/pilot named Jim Tatum donated the use of his private jet to shuttle Charlotte and Jordan to and from Brownsville, Texas (just across the border from Matamoras, Mexico and the Rio Valley Medical Clinic).

Readers can learn more about MLD by visiting this NIH website: http://www.ninds.nih.gov/disorders/metachromatic_leukodystrophy/metachromatic_leukodystrophy.htm

Like most things in medicine, there is a flip side to hUCSC therapy; which is to say, there are conditions that have responded poorly or not at all. Among these: advanced Multiple Sclerosis, middle-to-advanced stage Lou Gehrig's (ALS), advanced COPD (Emphysema), diabetes type I (No impact on insulin production or use), and Charco Marie Tooth Disease. However, not a single patient followed by SRI has gotten worse as a consequence of the treatment (Some have progressive diseases that by their very nature invite continued deterioration). And in many instances involving progressive diseases, patients had their condition stabilize and even improve for fairly long periods of time.

Although the overall response of patients to treatment with pure umbilical cord stem cells has been salutary, many challenges lie ahead. One of the more daunting ones concerns boosting patient response by getting stem cells to the target tissue or organ. These cells tend to home in on specific cytokine signals expressed by inflamed, infected and damaged tissues and organs. As such, it is important to make sure that these signals are coming from the target tissue or organs and not other sites in the patient's body. Generally, this requires an aggressive screening and pre-stem cell treatment program to quell signals in non-target tissues or organs and concomitantly amplify signals from the target tissues or organ. Also, as heavy metals and other factors can impair or even kill proliferating cells, these too must be eliminated prior to stem cell therapy. In addition, patients who have had injuries years prior have down regulated stem cell attraction molecules in the affected tissues. Thus when stem cells are given, often these people receive little benefit since the stem cells do not know where the damaged tissues are. On-going research is being conducted to determine what methods are best at getting healed up tissues and organs to once again begin churning out stem cell attraction molecules such as stromal derived factor-alpha. This, it is felt, will greatly improve clinical outcome in patients with, for example, heart or brain damage that occurred many years previously. SRI's director, Dr. David A. Steenblock, has made many pioneering inroads in terms of developing and fine-tuning protocols that get quiescent tissue to begin generating cytokine signals that hUCSCs will be attracted to, as well as programs for helping patients maximize stem cell engraftment, proliferation and subsequent activity. These are being offered through the auspices of his clinic in Mission Viejo, California (Brain Therapeutics Medical Clinic, 1-800-300-6063, www.strokedoctor.com)

In my home state of Texas, we have a saying that goes "if you see smoke coming from the woodpile, there's a fire burning somewhere therein." While the evidence concerning the efficacy of hUCSCs for non-hematopoeic diseases and conditions is tentative, we at SRI feel there is "smoke in the woodpile" coming from a biologic fire lit by these cells. And yes, in some instances the blind see and the lame walk. In terms of the promise and utility of hUCSCs to transform some areas of medical care in the future, this realm of science could indeed transform mythic feat into reality.

Want to learn more about human umbilical cord stem cells and hUCSC therapy?

* Check out SRI's 90 page handbook on hUCSCT--free and online at http://14ushop.com/wizard/HB082505.pdf

* Visit www.stemcelltherapies.org

* Come March 2006, pick up a copy of "Human Umbilical Cord Stem Cell Therapy: The Gift of Healing from Healthy Newborn Babies" by David A. Steenblock, DO and Anthony G. Payne, PhD (Basic Health Publications). This book will be available on www.basichealthpub.com and www.amazon.com.

Background on Dr. Payne:

Anthony G. Payne, MA, PhD, MD (hon.) is staff biological theoretician at the Steenblock Research Institute. Dr. Payne holds earned undergraduate and graduate degrees in biological anthropology, plus doctorates in nutritional medicine and psychology. Prior to joining SRI, Dr. Payne spent over 4 years teaching university in Japan. He is 20+ year member of the international genius society MENSA, and a Bureau of Indian Affairs certified American Indian and tribal member of the Choctaw Nation of Oklahoma (www.choctawnation.com). He and his wife, Sachi, live in sunny southern California.

Correspondence:

Anthony G. Payne, PhD

Steenblock Research Institute

949-248-7034

biotheoretician@gmail.com

by Anthony G. Payne, PhD, MD (hon.)

Steenblock Research Institute, San Clemente, California (USA)

RELATED ARTICLE: The Korea Times

November 26, 2004

"Embryonic stem cells are omni-potent in that they can divide into any thing even including a tumor cell. But cord blood stem cells are developed enough not to cause such troubles while retaining as powerful a differentiation capacity at the same time," he claimed.

"Another upside of cord blood stem cells is that they can adapt to the injected bodies without triggering a big negative inner reaction, which are common in other transplantations," according to Han, Ph.D, of the SCB (Dr. Han Hoon of the Seoul Cord Blood Bank)

"We don't need a strict match between cord blood stem cell type and the immune system of a patient because the latter accepts the former pretty well thanks to its immaturity," Han said.

"Korean Scientists Succeed in Stem Cell Therapy" By Kim Tae-gyu, Staff Reporter

http://times.hankooki.com/lpage/200411/kt2004112617575710440.htm

RELATED ARTICLE: In a Nutshell: Cord Blood-derived Stem Cells

They are isolated from cord blood, hence there are no red or white cells present. This virtually eliminates the need for blood typing or HLA matching.

They are safe, because there is no graft versus host or rejection issues (as is the case with whole cord blood).

No immunosuppressant drugs are needed.

Best responders (so far): Cerebral palsy, traumatic brain injury, diabetic retinopathy and neuropathy, early stage progressive and secondary progressive multiple sclerosis, and Lou Gehrig's disease.

Poor responders (so far): Advanced multiple sclerosis and Lou Gehrig's disease, advanced COPD (emphysema), Charco Marie Tooth disease and diabetes type I (Insulin production and utilization).

Diseases for which insufficient patient response data exists yet to determine efficacy of hUCSCT: Parkinson's disease, Alzheimer's disease, retinitis pigmentosa, and a host of other eye, circulatory, neurologic and other diseases and conditions.

RELATED ARTICLE: SRI: The Little Nonprofit Institute That Could

* Founded 2003. Staff of 2, now 7

* 12,000+ vol. medical & scientific library

* Developed USPTO Patent Pending protocols for pre- and post-hUCSC therapy

* Has accrued data and case history documentation on over 125 patients treated with hUCSCs (in Mexico)

* Asked by the White House to provide input on human umbilical cord stem cells to President Bush (October 2004)

* Is providing technical support & data analysis to those involved in doing the world's first use of gene transvected hUCSCs to treat the terminal neurologic condition Metachromatic Leukodystrophy

COPYRIGHT 2005 The Townsend Letter Group
COPYRIGHT 2006 Gale Group

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