Acetylcarnitine from Montiff

NYBC has been working with this company for some time. The NYBC product that we had was from them, via the contract manufacturing of “mass quantities” through DAAIR. We had that material tested at an independent lab and it came through fine.

This link provides some additional information on the product, which is included as part of the Mac Pack. Don’t forget that if you are suffering from neuropathy, the data from Youle’s study suggest a higher dose may be necessary.

http://www.aminoacidbotanicalandsupplementsource.net/N-Acetyl-L-Carnitine%20HCL_info.htm

Who owns Glycobiology?

A recent article in Science (2 Nov 07(318):734-737) discussed the wealthy Mannatech company that produces aloe-based products such as Acemannan. It has long been used as one of the many alternative approaches to managing HIV infection.  Sugars (carbohydrates) are often found in the body attached to fats (lipids) or proteins where they are known as glycolipids or glycoproteins. As a field of scientific discovery, this is a relatively new area of understanding biological systems and functioning.

Some scientists in the field have taken umbrage against Mannatech for commercializing products that are little understood and applying a patina of science to their own sales efforts. While the science is definitely critical, company-sponsored research is always questionable. With agents like dietary supplements, we suffer the double whammy of little financial interest in paying for these studies due to lower profits as well as lack of interest on the part of mainstream medicine.

However, Mannatech is a well-heeled company, charges a great deal (with a workforce of 500,000 independent sales people according to the article) and some $400 million in sales, they are hardly poor, if not as stinking rich as even relatively small pharmaceutical companies. At issue is a scientific conference that Mannatech has provided some funding for. This conference on glycobiology to take place in Ireland has some scientists up in arms.

Essentially, paid for conferences of this type ARE problematic. The pharmaceutical industry has virtually completely replaced continuing physician education with dog and pony shows designed solely to sell product, while downplaying side effects. (An article from the November 25, 2007 New York Times on the topic is illustrative.)

Unfortunately, there is only one significant study of Acemanna in the context of HIV (J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jun 1;12(2):153-157) which found no benefit in terms of CD4 count nor in the older p24 antigen assay (prior to viral loads and not very useful as a marker).  The abstract is below.

But this leaves us in a bind. How do we get good data on these types of interventions? How can we figure out what works, what helps? And how can we establish the cost/benefit of such interventions? Perhaps a new administration will reinvigorate the NIH so that more independent studies can be undertaken of the most important questions.

Sadly, the for-profit, privatized approach to discovery, let alone access, has left us with fewer reliable data, misinformed physicians and reduced access to best practices and care.

George M. Carter

Abstract:

Montaner JS, Gill J, Singer J, Raboud J, Arseneau R, McLean BD, Schechter MT, Ruedy J.

Canadian HIV Trials Network, St. Paul’s Hospital/University of British Columbia, Vancouver, Canada.

SUMMARY: We assessed the safety and surrogate markers’ effect of acemannan as an adjunctive to antiretroviral therapy among patients with advanced HIV disease receiving zidovudine (ZDV) or didanosine (ddI) in a randomized, double-blind, placebo-controlled trial of acemannan (400 mg orally four times daily). Eligible patients of either sex had CD4 counts of 50-300/microl twice within 1 month of study entry and had received 26 months of antiretroviral treatment (ZDV or ddI) at a stable dose for the month before entry. CD4 counts were made every 4 weeks for 48 weeks. P24 antigen was measured at entry and every 12 weeks thereafter. Sequential quantitative lymphocyte cultures for HIV and ZDV pharmacokinetics were performed in a subset of patients. Sixty-three patients were randomized. All were males (mean age 39 years). The mean baseline CD4 counts were 165 and 147/microl in the placebo and acemannan groups, respectively; 90 percent of the patients were receiving ZDV at entry. Six patients in the acemannan group and five in the placebo group developed AIDS-defining illnesses. There was no statistically significant difference between the groups at 48 weeks with regard to the absolute change or rate of decline at CD4 count. Among ZDV-treated patients, the median rates of CD4 change (ACD4) in the initial 16 weeks were – 121 and – 120 cells per year in the placebo and acemannan groups, respectively ( p = 0.45), ACD4 from week 16 to 48 was 0 and – 61 cells per year in the acemannan and placebo groups (p = .11), respectively. There was no statistical difference between groups with regard to adverse events, p24 antigen, quantitative virology, or pharmacokinetics. Twenty-four patients, 11 receiving placebo and 13 receiving acemannan, discontinued study therapy prematurely, none due to serious adverse reactions. Our results demonstrate that acemannan at an oral daily dose of 1600 mg does not prevent the decline in CD4 count characteristic of progressive HIV disease. Acemannan showed no significant effect on p24 antigen and quantitative virology. Acemannan was well tolerated and showed no significant pharmacokinetic interaction with ZDV.

 

Low Platelets Treated with Danazol

Danazol Increases Platelet Counts in Thrombocytopenia Patients with Chronic Hepatitis C or Cirrhosis: presented at AASLD

 

By Maria Bishop

http://www.docguide.com

 

BOSTON, MA — November 5, 2007 — Patients receiving the standard treatment of pegylated interferon alfa 2a plus ribavirin for chronic hepatitis C virus (HCV) may become thrombocytopenic, but are able to achieve increased platelet counts through danazol therapy, according to research presented here at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

 

This is the first report of using a novel alternative treatment for thrombocytopenia in this difficult patient population, noted lead author, Guillermo Cabrera-Alvarez, MD, Gastroenterology and Liver Department, Internal Medicine Division, Regional General Hospital – Family Medicine Unit #1, Mexican Social Security Institute, Cuernavaca, Morelos, Mexico.

 

Dr. Cabrera-Alvarez and colleagues conducted an open-label clinical trial of 41 danazol-na•ve patients with chronic HCV (90% with cirrhosis of the liver), who had developed thrombocytopenia as a result of treatment with pegylated interferon alga 2a plus ribavirin. The treatment group (n = 26, 20 female) received danazol at 300-600 mg/day until the end of the HCV therapy. Fifteen control subjects (9 females) were matched for baseline platelet count, presence of cirrhosis, age, sex, and HCV genotype, but were not considered thrombocytopenic.

 

The mean baseline platelet count for treated patients was 75,300 ± 11,502, which was increased at the end of the study to 123,900 ± 30,411 (P =.0063) in the 23 patients available for evaluation (20 females).

 

Of those 23 danazol-treated patients, 4 were considered non-responders, 7 were mild responders, and 12 were considered to have had a good response. Efficacy was evaluated as the capacity to increase platelet counts until the end of the treatment period.

 

In the control group (non-thrombocytopenic), the mean platelet count went from 238,953.3 ± 141,962.9 at baseline to 174,200 ± 91,643 at end of treatment (P =.9246).

 

Only two danazol-treated patients developed reversible cholestasis, noted Dr. Cabrera-Alvarez. No other patients presented with side effects.

 

“We believe that maybe [the mechanism of action] involves impairment of macrophage-mediated clearance of antibody-coated platelets via decreased Fc receptor expression, as in autoimmune thrombocytopenia,” said Dr. Cabrera-Alvarez. Danazol has been used successfully to treat patients with autoimmune thrombocytopenia.

 

Danazol is a derivative of the synthetic steroid ethisterone, a modified testoterone. This drug decreases the follicle-stimulating hormone and luteinizing hormone. Liver function must be monitored on a periodic basis in patients receiving long-term therapy with danazol, as it is metabolised by the liver.

 

 

[Presentation title: Danazol Increases the Platelets Count in Thrombo-Cytopenic Patients with Chronic Hepatitis C and Liver Cirrhosis Treated With Peg-Interferon Alfa 2a and Ribavirin. Abstract 260]

 

ABSTRACT

 

Danazol Increases the Platelets Count in Thrombo-Cytopenic Patients with Chronic Hepatitis C and Liver Cirrhosis Treated With Peg-Interferon Alfa 2a and Ribavirin.

 

G. Cabrera-Alvarez1; L. Ca–edo-Dorantes2; J. Reyes-Esparza3; L. Rodr’guez-Fragoso3; N. Mendez-Sanchez5; A. Burguete4; V. Madrid-Marina4

1. Gastroenterology, IMSS, Cuernavaca, Morelos, Mexico.

2. Faculty of Medicine, Postgraduate Division, Universidad Aut—noma del Estado de Morelos, Cuernavaca, Morelos, Morelos, Mexico.

3. Faculty of Pharmacology, Universidad Aut—noma del Estado de Morelos, Cuernavaca, Morelos, Morelos, Mexico.

4. Chronic Infections and Cancer Division, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Morelos, Mexico.

5. Liver Unit, Medica Sur Clinic & Foundation, Mexico city, MŽxico, Mexico.

 

Background and Aim: Chronic hepatitis C (HCV) infection has been associated with the development of several extrahepatic alterations, including thrombocytopenia. Currently it remains unresolved. Danazol, an attenuated androgen has been succesfully used in patients with autoimmune thrombocytopenia. The aim of the present study was to investigate the effects of Danazol treatment for thrombocytopenia associated to peginterferon alfa-2a and ribavirin therapy in na•ve HCV patients.Ê

 

Methods: A prospective study carried out in patients with chronic hepatitis C or liver cirrhosis patients who were under antiviral therapy. The protocol was approved by the Review Board/Ethics committee of the Hospital. The inclusion criteria including both gender, age (20 to 70 yr), without co-infection with hepatitis B virus or human immunodeficiency virus (HIV-1/2), thrombocytopenia during peginterferon alfa-2a and ribavirin therapy was defined when the count was ² 90,000 platelets/mL in the last month. Danazol 300-600 mg/day was administered until the end of therapy. We considere as a control patients those on antiviral therapy who did not receive adjuvant danazol due to only mild thrombocytopenia on antiviral therapy, matched for baseline platelet count, presence of cirrhosis, age, sex and HCV genotype. Efficacy was evaluated as the capacity to increase in platelet counts until the end of the treatment period.Ê

 

Results: A total of 41 patients with HCV-associated thrombocytopenia with PEG IFN/ribavirin treatment were studied: 26 patients (20 females, 6 males), mean age of 54.57± 8.40 yr who received danazol and 15 controls (9 females, 6 males), mean age of 55.8 ± 13 yr. Ninety percent of 41 patients had cirrhosis and the HCV genotypes were similar between groups. The platelet count increases in the Danazol group from baseline (75300 ± 11502) after treatment (123,900 ± 30411 p=0.0063). Whereas in the control group the mean count range from (238953.3 ± 141962.9 to 174200± 91643, p=0.9246) respectively. No association between genotypes and thrombocytopenia was observed (P>0.05). Danazol safety was assessed by the absence of collateral negative effects, except colestasis reversible in two patients.Ê

 

Conclusions: Adjuvant use of Danazol is associated with increased platelets counts in patients on antiviral therapy with interferon and rivabirin for HCV infection and cirrhosis. This is new therapeutic option to treat thrombocytopenia and maximize the sustained virologic response.