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For the newbies Nicosan is also Niprisan, also Hemoxin also NIX-0699 as it relates to the studies.
This is an e-mail response from the director of SCD Research at the Children's Hospital of Philadelphia. He has had clsoe involvement in the support of Xecehm , Nicosan and 5-HMF.
All of this affords EXTREME credibility to the Xechem foundation of Nicosan and 5-HMF. These studies would not have been done, hours spent, dollars expended, etc. if there was NOT potential for htese to have a potneitl effect on the SCD environment. These people don't care about stock price, PPS, revenues, etc. They care about resolving SCD.
----- Original Message -----
From: Toshio Asakura
To: Jim
Sent: Thursday, September 28, 2006 6:17 AM
Subject: Re: Nicosan - Hemoxin
> The papers related to NIPRISAN are:
> 5. Iyamu EW, Turner and Asakura. In vitro effects of NIPRISAN: a
> naturally occurring, potent antisickling agent. Brit J Haematol 118:
> 337-343, 2002
>
> 6. Iyamu, EW, E. A. Turner, Asakura, T. NIPRISAN (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe
> hypoxic conditions. Br. J. Haematol. 122: 1001-8, 2003.
> Toshio Asakura M.D., Ph.D.
>
> These potential treatments are promising and become more so as more >research is accomplished supported by resultant data.
>Dr. Toshio Asakura
>>>> Jim
09/26/06 5:20 PM >>>
> Good Afternoon Doctor;
>
> I have found some papers in the recent past where you published/were
> involved in the study of Nicosan, but I cannot find any specific
> references to the research data.
>
> Is there any available you can point me too? or can you give me
> some insight as to the potential of the Herbal Drug to support it's
> claims of SCD efficacy treatment.
>
> I appreciate your time , in advance.
>
> Sincerely;
> Jim
Importance of Quality Control In the Development of Herbal Medicines as Drugs: The Antisickling Phytopharmaceutical Niprisan/NICOSANTM/HEMOXINTM
1Peter N. Gillette, MD, 2Renuka Misra, PhD, 2Prema Tripathi, BHMS,
3Toshio Asakura, MD, PhD, 2Ramesh C. Pandey, PhD
1State University of New York at Brooklyn; 2Xechem Research Laboratory, New Brunswick, N.J.;
3Children's Hospital of Philadelphia
The new antisickling drug Niprisan (Nix-0699, NICOSANTM, HEMOXINTM) is a modern preparation based on a traditional phytopharmaceutical from Nigeria. It is an extract of a mixture of four plants administered by healers to reduce pains of Sickle Cell Disease especially in children and adolescents. In laboratory studies it strongly inhibits sickling of red blood cells, and it benefits patients in Nigerian clinical trials. US trials await final standardization of the product.
Niprisan development has revealed three links with medications used by India's traditional healers in the 5000 year old Vedic Herbal System “Ayurveda”: administration by healers, herbal source, and decoction of multiple plants. This paper will describe laboratory and clinical studies of Niprisan and discuss methods to overcome the difficulties in preparation and standardization of phytopharmaceuticals.
Interestingly, initial standardization of Niprisan showed that all four botanicals contribute to efficacy. By several different approaches including high performance liquid chromatography (HPLC), fractionation and subsequent recombination of various fractions reduces potency (Asakura; Pandey; unpublished data) as is true for many botanicals.
There is a striking analogy between the lessons being learned from working with a traditional medicine and challenges for the future of herbal medicines such as those used in Ayurvedic phytomedicine.
5-HMF
It is also very active in genetically modified mice as shown by Dr. Toshio Asakura, Director, and his colleagues at the NIH-NHLBI Sickle Cell Disease Reference Laboratory at the Children's Hospital of Philadelphia, University of Pennsylvania
Childrens Hosp Philadelphia, Div Hematol, Abramson Pediat Res Ctr, Philadelphia, PA 19104 USA.
ProHlth Med Ctr, Franklin, TN USA.
Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
Reprint Iyamu, EW, Childrens Hosp Philadelphia, Div Hematol, Abramson Pediat
Res Ctr, 3516 & Civ Ctr Blvd,Room 314 I, Philadelphia, PA 19104 USA.
Abstract Among the various potential antisickling agents tested, hydroxyurea (HU) has been the most effective compound used for the treatment of patients with sickle cell disease (SCD). Although HU is effective in many patients, not all patients respond to this drug. In addition, some patients reveal adverse effects, including myelosuppression. In an attempt to find other effective agents with less adverse effects, we investigated the antisickling effect of NIPRISAN (Nix-0699). We found that Nix-0699, an ethanol/water extract from indigenous plants, has a strong antisickling effect. The concentration of Nix-0699 required to inhibit 50% of erythrocyte sickling was about 0.05 mg/ml. As for the kinetics of polymerization, addition of 0.05 mug/ml Nix-0699 caused a sixfold prolongation of the delay time prior to deoxy-Hb S polymerization when compared with that of untreated Hb S samples. The solubility of deoxy-Hb S significantly increased upon treatment with Nix-0699. Analysis of the effect of Nix-0699 on the Hb S oxygen affinity indicated that the drug slightly shifted the oxygen-dissociation curve of Hb S toward the left without any apparent change in the Hill coefficient. These results suggest that the antisickling properties of Nix-0699 may involve direct interaction with Hb molecules. Incubation of red blood cell (RBC) suspensions with various concentrations of Nix-0699 did not dehydrate RBCs, cause haemolysis, increase the amount of denatured Hb, nor form met-Hb. In view of the outcome of this study, Nix-0699 may be a promising option for the treatment of patients with SCD.
Childrens Hosp Philadelphia, Div Hematol, Abramson Pediat Res Ctr, Philadelphia, PA 19104 USA.
ProHlth Med Ctr, Franklin, TN USA.
Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
Reprint Iyamu, EW, Childrens Hosp Philadelphia, Div Hematol, Abramson Pediat
Res Ctr, 3516 & Civ Ctr Blvd,Room 314 I, Philadelphia, PA 19104 USA.
Abstract Among the various potential antisickling agents tested, hydroxyurea (HU) has been the most effective compound used for the treatment of patients with sickle cell disease (SCD). Although HU is effective in many patients, not all patients respond to this drug. In addition, some patients reveal adverse effects, including myelosuppression. In an attempt to find other effective agents with less adverse effects, we investigated the antisickling effect of NIPRISAN (Nix-0699). We found that Nix-0699, an ethanol/water extract from indigenous plants, has a strong antisickling effect. The concentration of Nix-0699 required to inhibit 50% of erythrocyte sickling was about 0.05 mg/ml. As for the kinetics of polymerization, addition of 0.05 mug/ml Nix-0699 caused a sixfold prolongation of the delay time prior to deoxy-Hb S polymerization when compared with that of untreated Hb S samples. The solubility of deoxy-Hb S significantly increased upon treatment with Nix-0699. Analysis of the effect of Nix-0699 on the Hb S oxygen affinity indicated that the drug slightly shifted the oxygen-dissociation curve of Hb S toward the left without any apparent change in the Hill coefficient. These results suggest that the antisickling properties of Nix-0699 may involve direct interaction with Hb molecules. Incubation of red blood cell (RBC) suspensions with various concentrations of Nix-0699 did not dehydrate RBCs, cause haemolysis, increase the amount of denatured Hb, nor form met-Hb. In view of the outcome of this study, Nix-0699 may be a promising option for the treatment of patients with SCD.
Br J Haematol. 2003 Sep;122(6):1001-8. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions.
Iyamu EW, Turner EA, Asakura T.
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA. iyamu@email.chop.edu
The substitution of glutamic acid by valine at the sixth position of the beta-globins of haemoglobin S (Hb S) causes a drastic reduction in the solubility of the deoxy form of Hb S. Under hypoxic conditions, deoxy-Hb S molecules polymerize inside the cells, forming rigid, sickled cells. We studied the effect of Niprisan (Nix-0699), a naturally occurring antisickling agent, on the survival of transgenic (Tg) sickle mice under severe acute hypoxic conditions (60 min). Before hypoxia exposure, the mice were treated by gavage once daily for 7 d with 0 mg/kg (n = 10), 10 mg/kg (n = 5), 50 mg/kg (n = 5), 300 mg/kg (n = 4) or 500 mg/kg (n = 5) of Nix-0699. The mean survival times of the untreated and treated mice were 10, 25, 39, 55 or 60 min respectively. The percentage of sickled cells in the venous blood of the treated mice was lower than that in control mice and was dose dependent. Histological examination of the lungs of the control mice showed entrapment of massive numbers of sickled cells in the alveolar capillaries, although the degree of such entrapment decreased with the increased dose of Nix-0699. Nix-0699 may be a promising option for the treatment and management of patients with sickle cell disease.
Br J Haematol. 2005 Feb;128(4):552-61. Links
5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells.Abdulmalik O, Safo MK, Chen Q, Yang J, Brugnara C, Ohene-Frempong K, Abraham DJ, Asakura T.
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. abdulmalik@email.chop.edu
In an attempt to find new types of anti-sickling agents that specifically bind to intracellular sickle haemoglobin (HbS) without inhibition by plasma and tissue proteins or other undesirable consequences, we identified 5-hydroxymethyl-2-furfural (5HMF), a naturally occurring aromatic aldehyde, as an agent that fulfils this criterion. Preliminary studies in vitro showed that 5HMF forms a high-affinity Schiff-base adduct with HbS and inhibits red cell sickling by allosterically shifting oxygen equilibrium curves towards the left. Further studies with transgenic (Tg) sickle mice showed that orally administered 5HMF was rapidly absorbed into the bloodstream from the gastrointestinal tract without being destroyed, traversed the red blood cell membrane and specifically bound with, and modified, HbS molecules at levels as high as 90%. Pretreatment of Tg sickle mice with 5HMF inhibited the formation of sickle cells and significantly prolonged survival time under severe hypoxia, compared with untreated mice, which died within 15 min because of sickling-dependent pulmonary sequestration. These results indicate the feasibility of 5HMF as an attractive potential candidate for therapy of sickle cell disease.
J Med Chem. 2004 Sep 9;47(19):4665-76. Links
Structural basis for the potent antisickling effect of a novel class of five-membered heterocyclic aldehydic compounds.Safo MK, Abdulmalik O, Danso-Danquah R, Burnett JC, Nokuri S, Joshi GS, Musayev FN, Asakura T, Abraham DJ.
Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23298, USA. msafo@mail2.vcu.edu
Naturally occurring five-membered heterocyclic aldehydes, including 5-hydroxymethyl-2-furfural, increase the oxygen affinity of hemoglobin (Hb) and strongly inhibit the sickling of homozygous sickle red blood (SS) cells. X-ray studies of Hb complexed with these compounds indicate that they form Schiff base adducts in a symmetrical fashion with the N-terminal alphaVal1 nitrogens of Hb. Interestingly, two cocrystal types were isolated during crystallization experiments with deoxygenated Hb (deoxyHb): one crystal type was composed of the low-affinity or tense (T) state Hb quaternary structure; the other crystal type was composed of high-affinity or relaxed state Hb (with a R2 quaternary structure). The R2 crystal appears to be formed as a result of the aldehydes binding to fully or partially ligated Hb in the deoxyHb solution. Repeated attempts to crystallize the compounds with liganded Hb failed, except on rare occasions when very few R state crystals were obtained. Oxygen equilibrium, high performance liquid chromatography (HPLC), antisickling, and X-ray studies suggest that the examined heterocyclic aldehydes may be acting to prevent polymerization of sickle hemoglobin (HbS) by binding to and stabilizing liganded Hb in the form of R2 and/or various relaxed state Hbs, as well as binding to and destabilizing unliganded T state Hb. The proposed mechanism may provide a general model for the antisickling effects of aldehyde containing small molecules that bind to N-terminal alphaVal1 nitrogens of Hb. The examined compounds also represent a new class of potentially therapeutic agents for treating sickle cell disease (SCD).
http://ocw.mit.edu/NR/rdonlyres/Biology/7-03Fall-2004/CCD5BFDE-9E3D-42AD-B941-3E44FA6BA778/0/lecture...
It is possible that the loan approval is waiting for Chassman to be done.
That was the chili he had at lunch...
Yes, where the Wisconsin River meets the Mississippi...:O)
Two IND's
NICOSAN™ is Xechem's name for the non-toxic phyto-pharmaceutical product formerly named NIPRISAN™. Xechem is currently in the process of completing for submission of an Investigational New Drug Application ("IND") for this product to the United States Food and Drug Administration ("FDA").
We are also preparing the Investigational New Drug (IND) application for 5-HMF for submission to the FDA in the coming months."
For those that don't Beleive that the US is a viable market for Nicosan:
Each year in the US, an average of 75,000 hospitalizations are due to Sickle Cell Disease, costing approximately $475 million. The average length of stay per hospital visit was 6.1 days and adults tended to have longer stays than children and adolescents.
-----Original Message-----
From: Jim
Sent: Tuesday, September 12, 2006 1:08 PM
To: breakingnews@andnetwork
Subject: Nigerian News for your paper
Can you let me know if you publish it. Thanks
Jim
September 12, 2006 07:30 AM Eastern Time
Xechem Chairman, Dr. Ramesh Pandey, to Present NICOSAN(TM) Story at 34th Annual SCDAA Conference in Dallas
NEW BRUNSWICK, N.J.--(BUSINESS WIRE)--Sept. 12, 2006--Xechem International, Inc. (OTC BB: XKEM) announced today that its Chairman and CEO, Dr. Ramesh C. Pandey, has accepted an invitation to make a presentation on NICOSAN(TM),
Responses:
-----Original Message-----
From: "tumelo@andnetwork-.-com"
Sent: Wednesday, September 13, 2006 1:26 AM
To: Jim
Subject: Return Receipt (displayed) - Nigerian News for your paper
-----Original Message-----
From: "mahap@andnetwork-.-com"
Sent: Wednesday, September 13, 2006 12:48 AM
To: Jim
Subject: Return Receipt (displayed) - Nigerian News for your paper
-----Original Message-----
From: "ntakisha@andnetwork-.-com"
Sent: Wednesday, September 13, 2006 1:27 AM
To: Jim
Subject: Return Receipt (displayed) - Nigerian News for your paper
-----Original Message-----
From: "kabwe@andnetwork-.-com"
Sent: Wednesday, September 13, 2006 1:33 AM
To: Jim
Subject: Return Receipt (displayed) - Nigerian News for your paper
About 500.
Xechem International is currently in the process of preparing an Investigational New Drug (IND) Application for Nicosan/Hemoxin for submission to the United States Food and Drug Administration (FDA) and applicable EU agencies. Nicosan/Hemoxin has received orphan drug status in the USA and Europe.
SCDAA said in an e-mail "SCDAA would not make a formal announcement before the drug has FDA approval or before it has been approved by the clinical trials consortium. We have allowed some time on the program for a representative from Xechem to speak on a panel about new therapies. Our conference is about education, so we feel everyone should hear the information and be able to make informed decisions about their care or the care of their loved one."
BUT, the more people involved , the more exposure, the more substantiation of the test results ("The Company will also set up a poster presentation during the Conference that will afford Xechem the opportunity to present to delegates the credible scientific and medical data that demonstrate both the efficacy and non-toxicity of NICOSAN(TM) (named HEMOXIN(TM) in the US") The process of approval in the US will expand and accelarate. This can only be good, and her input can only be good.
I have also requested the abstract of the Xechem presentation after the conference. Also, my contact said that she would forward me her comments and input of the presentation and how it was received by the "masses" at the conference. I will post it when I receive it.
Having been the one to start this foray of "Conference" mania, please remeber, DD, contacts with those in the industry (of which the information about attending the conference came) is invaluable. From the info my contact gave me, we were able to "pursuade" Xechem to PR the event. In these situations, it really puts bashers in their place, they cannot argue these facts. I am sending my contact a VERY warm THANK YOU for passing the info onto me.
GLT Everyone.
I was told by my contact at Children's Hospital of Philadelphia, that you can request a copy of the Abstract document for the conference after the event. I have requested this document. Unless it's $1000.00 :O)
I would love to attend and here these details.
• ABSTRACT TEXT: Abstract content should be single spaced, typed in lower case (10-12 pt font) and structured according to the presentation as follows:
1. Standard Research Format
• Objective of Purpose
• Method
• Results
• Conclusions
2. Educational
• Overview and Background
• Program and/or Learning Objectives
• Methods of Instruction and/or Administration
• Progress and/or Results to date
• Plans/Consideration for continuation
3. Innovative Program or Service
• Overview and Background
• Unique features or characteristics
• Who/How is it implemented
• Progress and/or results to date
• Plan(s)/Consideration(s) for continuation
4. Management of Administrative Strategies
• Description of Problem(s) or Issue(s)
• Management of Administrative Strategy(ies)
• Final Analysis or Conclusion
I have comfirmed (for myself) that Xechem will indeed be presenting at the 34th Annual SCDAA conference on Friday Sept. 29th from 4:00 p.m. to 5:00 p.m. as part of the "Simultaneous Sessions". Also, they will be participating in the "Plenary Panel" hosted by the Children's Hospital of Philadelphia at 8:30 a.m.
It will be Dr. Pandey that will be speaking.
1-800-421-8453; Sterling
WE MUST GET XKEM TO PR THIS.............. anyone?
I asked if you had to be a member of one of the member organizations to attend, and he said no, I would have to pay the full registration price even just to attend these two sessions. But an average Joe like me is welcome and encouraged to attend.
Also, they must have known about this all along, becuase the deadline to present was June 16th, 2006 Hmmmmmmmmm
SICKLE CELL DISEASE ASSOCIATION OF AMERICA, INC.
34th Annual Convention
CALL FOR ABSTRACTS
Authors interested in presenting data should submit an abstract using the form in this program. All approved abstracts will be published in the final program to be distributed to attendees of the conference.
Acceptance notification and further instructions will be e-mailed on July 28, 2006. All correspondence will be sent to the name and e-mail address on the abstract form.
DEADLINE: Friday, June 16, 2006
Wrong Scarecrow. Please stop your playing. You have been presnted with a lot of information to confirm the conference attendance. They will not be listed, as others are not listed either. Stop distorting the facts. You have been called on the carpet on many other boards, but you cannot own up. You are wasted breath.
Yes, I do. I understand we are one step closer to the line up ..... But I prefer to keep my "judgements" to myself, and only post facts and data. If I were to post my true feelings it would be....... WOOOOOHOOOOOO !!!! :O) :O)...... But then again I am a calm kinda guy... :O) I also beleive there are several things in the works that hinged on the final FCC grant... GLTA...
There is always a lot of emotion when volume that is unexpected and unjustified by news, happens. A lot of perceptions and posts results from personal "I want's or I wish's and hopes". I would like to thank the posters here that have presented information based on an analysis of the trading, volume, and history. There are several seasoned investors here that know, based on experience, that this volume and trading performance happens/ed because of "something" and they post it here. There are those that offer swayed information, misquoted information in support of their personal "needs of this stock to perform", either upward or downward (i.e. pumpers and bashers). Seasoned investors see through it, take the meat and add it to their analysis. Novice and new investors, have not learned, and soak up the emotional posting. DD is of utmost importance here, if I could give anyone advice. There are two facts 9comprised of many items).
1.) Company performance in obtaining contracts FOR WHATEVER REASON/s, is lacking. We all know the end results we, and the company want and need, is revenues. For whatever reasons this has not happened yet, and we could debate all day why. If you have done your DD, you will see that it is 75% arena and politics related. The other 25% is the company learning curve about getting into this market. The lessons learned will make them a formidible force to deal with once they enter market.
2.) They have worked to obtain total system approval by FCC. They have sumbitted many RFP applications. They have learned form the lessons for some being turned down. We know CNES tech offers more than most AMR offerings. The differences lie in the entire system. CNES goes further, and utilizes software to allow billing to be done from the data. I.E, CNES becomes the utility billing center, customer billing issues center, information/data
verifier, response center to meter/ source issues, installation scheduler, meter / AMR tech maintenance and repair, meter installer, etc.
This is where the revenues come in. The revenue is not in the technology or the meter. The revenue is in a percentage/royalty for performing these other services. We know they have approval for integration into GE, L&G and Sensus meters. We know they will have NOC shortly. We know MDMA is important in the AMR arena that is forming.
"Over the past few years, there has been a clear transition from the classic AMR approach to advanced meter management (AMM). The transition has been driven by both technological and data management considerations. The biggest single technological change that has enabled this transition is the added functionality made possible by bidirectional communication to the meter endpoints. While receiving reads from the meters is still clearly the biggest change and provides the largest perceived benefit for the utility, significant benefits can be obtained from the new functionalities provided by this technological advance. Additionally, in many cases the tools to perform analyses using information from the meter data warehouse were never implemented or did not meet the vision of what was intended. This has led to a number of companies that had previously implemented AMR to now look at implementing a fully functional meter data management (MDM) system to realize that vision. " Quoted from an article previously posted.
We know they are doing a redesign to reduce the number of boards from 3 to 2. Why? If you have done your DD and read the 10K, you will see gas meters mentioned. They have outlined in the 10K expansion into other AMR areas. We know that they have SCE approval to expand the pilot. As previously posted, SCE is involved, as they must approve the meter change and monitoring. We know they did not recieve the CSU RFP, for inability to do water and gas meters, hence the redesign?? We know they are developing a business plan, if you glean the 10K, you can begin to see where they are heading. I could go on and on.
So, look at the supporting evidence.
Lack of a contract.... Many areas of potential with supporting evidence..... and the volume and share price traded Friday... 2 + 2 = ......
Please wade through the crap and innuendo and find the meat. And remember the number one rule... it's all 50 / 50 until it happens... until it is public... GLTA.
I posted this on RB earlier. I welcome your comments and input.
10K is also out.
Let's ALL just not reply to him AT ALL. It will irritate him. and we won't waste space. :O)
"E" should be off "in a few days", was the response from CNES yesterday. They also said they will release the PR on the FCC when the "E" is off. FYI only. I am assuming to release the PR on the FCC when the E is there, may cause some new investors to be "shy".
The total shares outstanding for Conectisys as of 1-19-2006 is
8,945,816,280
since last update, that is the difference.
OS Date Change since previous OS Update
8,222,521,732 1/6/06 392,833,233
Actually, I'm only new to this board. Been in CNES since NOV. 2004... came here because RB is getting ridiculous.. have 10 mil. at .00029 average... GLT everyone.
Let's hope Monday is a PR day. New here...