There are a new batch of papers that demonstrate statins' anti-inflammatory effect. Yes it's true. If you shut off your immune system, you won't have any inflammation! Yet, scientists have known for at least a decade that statins have a dose-dependent immunosuppression effect.
1: J Heart Lung Transplant. 1998 Apr;17(4):335-40.
The inhibitory effects of pravastatin on natural killer cell activity in vivo and
on cytotoxic T lymphocyte activity in vitro.
Katznelson S, Wang XM, Chia D, Ozawa M, Zhong HP, Hirata M, Terasaki PI,
Kobashigawa JA.
Division of Nephrology, University of California, Davis, School of Medicine,
Sacramento, USA.
BACKGROUND: We have reported that heart transplant recipients treated with pravastatin demonstrate decreases in the incidence of clinically severe acute rejection episodes, the incidence and progression of transplant coronary vasculopathy, and natural killer cytotoxicity. These patients also exhibited a significant improvement in 1-year allograft survival. Because of these clinical findings suggesting an immunosuppressive effect of pravastatin unique to transplant recipients and the unclear role of natural killer cells in allograft rejection, we postulated that pravastatin may exert its immunomodulatory effect by acting with cyclosporine to alter T lymphocyte function. METHODS: Twenty patients randomized into an ongoing trial of pravastatin after heart transplantation were monitored serially for natural killer cell cytotoxicity. In a separate experiment, lymphocytes isolated from normal volunteers were treated with various combinations of pravastatin and cyclosporine and tested for cytotoxic T lymphocyte toxicity in a one-way mixed lymphocyte reaction. RESULTS: Pravastatin-treated heart transplant recipients exhibited a decrease in natural killer cell cytotoxicity (9.8% mean natural killer cell cytotoxicity vs 22.1% in the control group, p < 0.01). In the one-way mixed lymphocyte reaction with blood obtained from control subjects, there was a synergistic inhibition of cytotoxic T lymphocyte activity when the cells were cultured in a combination of pravastatin and cyclosporine (20.3% mean cytotoxicity of target cells vs 41.4% in the control group, p < 0.01). CONCLUSIONS: Pravastatin exerts an immunosuppressive effect in heart transplant recipients as expressed by a reduction in rejection and natural killer cell cytotoxicity. Pravastatin and cyclosporine act synergistically to reduce cytotoxic T lymphocyte activity. This synergistic effect of pravastatin and cyclosporine may explain why this immunosuppressive effect is unique to transplant recipients.
PMID: 9588577 [PubMed - indexed for MEDLINE]
1: Drugs. 2002;62(15):2185-91.
HMG-CoA reductase inhibitors as immunomodulators: potential use in transplant
rejection.
Raggatt LJ, Partridge NC.
Department of Physiology and Biophysics, Robert Wood Johnson Medical School,
University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854,
USA.
The benefit of HMG-CoA reductase inhibitors (statins) to the cardiovascular system is now well established and these drugs are being used extensively to treat hypercholesterolaemia clinically. However, as clinical outcomes become available it appears that statins are proving more beneficial than expected and thus it is being proposed that the actions of statins go beyond their ability to lower serum cholesterol levels. The report that statins can interact directly with lymphocyte function-associated antigen (LFA)-1 and prevent it engaging with the intracellular adhesion molecule (ICAM)-1 receptor on T cells is a novel mechanism of statin action and provides convincing evidence that these compounds can regulate biological systems other than by the cholesterol synthesis pathway. Immunosuppression to prevent organ transplant rejection is one application for which statins are currently being assessed. The clinical evidence is conflicting and does not convincingly reflect whether statins are beneficial as immunomodulators. However, in vivo studies investigating the cellular actions of statins have identified two mechanisms by which statins can potentially modulate an in vivo immune response. Firstly, statins regulate inducible class II major histocompatibility complex (MHC) expression on macrophages and endothelial cells. Secondly, statins can inhibit LFA-1 adhesion to ICAM-1 and thus regulate T cell activation. These findings suggest that statins have the potential to regulate an immune response in vivo and that more investigation is essential in order to explain the opposing clinical data.
PMID: 12381218 [PubMed - indexed for MEDLINE]
1: Atheroscler Suppl. 2002 May;3(1):17-20.
Immunosuppressive effects of statins.
Mach F.
Medicine Department, Cardiology Division, Foundation for Medical Research, Geneva
Medical School, University Hospital, 64 Avenue Roseraie, 1211 Geneva,
Switzerland.
3-Hydroxy-3-methhylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are effective lipid lowering agents, extensively used in medical practice [Circulation 2000;101:207; J Am Med Assoc 2000;283:2935]. Statins have never been shown to be involved in the immune response, although reports have suggested a better outcome of cardiac transplantation in patients under pravastatin therapy [New Engl J Med 1995;333:621; Circulation 1997;96:1398]. Major histocompatibility complex class II (MHC class II) molecules are directly involved in the activation of T lymphocytes and in the control of the immune response. Whereas only a limited number of specialized cell types express MHC-II constitutively, numerous other cells become MHC-II positive upon induction by interferon-gamma (IFN-gamma) [Annu Rev Immunol 1996;14:301]. This complex regulation is under the control of the transactivator CIITA [Science 1994;265:106]. Recently, we demonstrated that statins act as direct inhibitors of induction of MHC-II expression by IFN-gamma and thus as repressors of MHC-II-mediated T cell activation [Nat Med 2000;6:1399; Swiss Med Wkly 2001;131:41]. This effect of statins is due to inhibition of the inducible promoter IV of the transactivator CIITA. Interestingly, this inhibition is specific for inducible MHC-II expression and does not concern constitutive expression of CIITA and MHC-II. In repressing induction of MHC-II, and subsequent T lymphocyte activation, statins therefore behave as a novel type of immunomodulator. This unexpected effect provides a scientific rationale for suggesting the use of statins as novel immunosuppressors, not only in organ transplantation but in numerous other pathologies as well.
PMID: 12044581 [PubMed - indexed for MEDLINE]
1: Swiss Med Wkly. 2001 Jan 27;131(3-4):41-6.
The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class
II expression in human vascular endothelial cells.
Kwak B, Mulhaupt F, Veillard N, Pelli G, Mach F.
Cardiology Division, Department of Medicine, University Hospital, Geneva Medical
School, Foundation for Medical Research, Geneva, Switzerland.
HMG-CoA reductase inhibitors, or statins, are lipid-lowering agents that have been shown to effectively decrease severe rejection periods and development of transplant coronary artery disease after heart transplantation. Precise regulation of major histocompatibility complex class II (MHC class II) gene expression plays a pivotal role in control of the immune response after transplantation. The aim of this study was to evaluate the potential role of HMG-CoA reductase inhibitors in regulating the immune response. We have examined the effects of simvastatin on MHC class II expression in primary human endothelial cells. Using RNAse protection assay and flow cytometry, we observed that simvastatin dose-dependently reduced interferon-gamma (IFN-gamma) induced MHC class II expression (mRNA and protein). In contrast, simvastatin did not affect the expression of MHC class I, pointing to specific actions in the MHC class II signalling cascade. The transcriptional coactivator CIITA is the general regulator of both constitutive and inducible MHC class II expression. After stimulation with IFN-gamma, the CIITA gene is selectively activated via one (promotor IV) of its four promoters. Interestingly, mRNA levels of CIITA were decreased after treatment with simvastatin. In addition, using transient transfections of promoter-reporter constructs we observed that the activity of CIITA promoter IV was decreased by simvastatin. In conclusion, simvastatin selectively decreases IFN-gamma-induced MHC class II expression in human primary endothelial cells through actions on the CIITA promoter IV. Thus, the beneficial effects of statins reported after heart transplantation may result from this immunosuppressive action, suggesting possible therapeutic use for other immunological disorders as well.
PMID: 11219190 [PubMed - indexed for MEDLINE]
1: Cancer Immunol Immunother. 2009 Mar;58(3):461-7. Epub 2008 Jun 4.
Potential immunologic effects of statins in cancer following transplantation.
Fildes JE, Shaw SM, Williams SG, Yonan N.
The Transplant Centre, University Hospital of South Manchester NHS Foundation
Trust, Wythenshawe Hospital, Manchester, UK. james.fildes@manchester.ac.uk
3-hydroxy-3-methyglutaryl CoA reductase inhibitors (statins) are frequently used following organ transplantation and have well reported pleiotropic effects, including immunomodulation, which may be of benefit in preventing graft rejection. However, the immunomodulatory effects of statins on cell transformation and malignancy, combined with the immunologic processes and administration of immunosuppression are almost completely unknown. The administration of immunosuppression is well recognised as the main cause of cancer following transplantation, so the addition of an immunomodulatory agent should be associated with an increased incidence of cancer, as immune surveillance and response may be suppressed, allowing cellular transformation and proliferation combined with lack of recognition to occur. This hypothetical review attempts to delineate the mode of action of statins in terms of pro/anti-carcinogenic mechanisms, while considering graft rejection and the presence of immunosuppression.
PMID: 18523769 [PubMed - indexed for MEDLINE]
Monday, August 31, 2009
More Evidence That Titles Do Not an Expert Make: Statins
I hate reading stuff like this because after all I started out wanting to make some good pills for peoples' health. More often than I like to read, these companies pawn useless stuff that causes another disease. It's cut and paste from http://www.hoptechno.com/statinsheets.htm
If the authors contact me, I'll gladly remove it but I can simply link to it. Perhaps the intentions were good in the beginning, but the disease misunderstood, and the outcome terrible, all the while the corporate fat cats lined their pockets at the expense of peoples' arteries. To me, that is more morbid and disturbing than a horror movie but I am sure plenty of people will come to the aid of the statin camp. The next post I have will be even more mind boggling.
"Cancer, Longevity and Statins
Do statins cause cancer or affect longevity?
Editor's note: The following are a sample of results of a search on the safety of statins (Cholesterol lowering drugs; e.g. Lipitor, Mevacor, Pravachol, Zocor).
It appears that:
1. there is a danger that statins cause cancer in humans
2. death rates in the population have not been reduced as a result of statin use
3. prescribing sheets show that statins cause liver cancer in animals.
Cancer: Source - Journal of the American Medical Association (JAMA) January 1996 The following is an extract.
Carcinogenicity of lipid-lowering drugs.
Newman TB, Hulley SB.
Department of Laboratory Medicine, School of Medicine, University of California, San Francisco, USA.
OBJECTIVE--To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs. DATA SOURCES--Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts. STUDY SAMPLE--We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans. DATA SYNTHESIS--All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up.
CONCLUSIONS--Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.
Death Rate. Source: http://www.drugintel.com/drugs/statins/statins_critical_review.htm - This link was taken down.
Besides cancer, the other side effects of statins listed were incomplete, and should have included constipation, myalgia, myopathy, polyneuropathy, liver and kidney damage, congestive heart failure and amnesia. Side-effects are usually said to affect 2-6% of patients. In fact, a recent meta-analysis noted side-effects in 20% of patients above the placebo rate (65% vs. 45%), and no change whatever in the all-cause death rate for atorvastatin (Lipitor). [8] The PROSPER trial on pravastatin (Pravachol) showed no change in the all-cause death rate, and increased cancer and stroke rates. [9] Statins are commonly used at a dose to lower TC to <160 mg/dL, a level noted in the report of a NHLBI conference to be associated with higher cancer rates.[10]
Footnotes:
[8] Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of Atorvastatin Derived from Analysis of 44 Completed Trials in 9,416 Patients. Am J Cardiol 2003;92:670-6.
[9] Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360(9346):1623-30.
[10] Jacobs D, Blackburn H, Higgins M et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation 1992:86:1046-60.
Death Rate: Source: Archives of Internal Medicine Vol. 153 No. 9, May 10, 1993 Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data http://archinte.ama-assn.org/cgi/content/abstract/153/9/1065
Conclusion: Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population.
The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years. The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above. [Ed: - low cholesterol = higher non-chd mortality; high cholesterol = lower; CHD = Coronary Heart Disease]
Prescribing sheets published by manufacturers of statin drugs (Oct 2005): [ALL of them mentioned liver cancer as a side effect]
Lipitor: In a 2-year carcinogenicity study in rats at dose levels of 10, 30, and 100 mg/kg/day, 2 rare tumors were found in muscle in high-dose females: in one, there was a rhabdomyosarcoma and, in another, there was a fibrosarcoma. This dose represents a plasma AUC (0-24) value of approximately 16 times the mean human plasma drug exposure after an 80 mg oral dose. A 2-year carcinogenicity study in mice given 100, 200, or 400 mg/kg/day resulted in a significant increase in liver adenomas in high-dose males and liver carcinomas in highdose females. These findings occurred at plasma AUC (0-24) values of approximately 6 times the mean human plasma drug exposure after an 80 mg oral dose.
Mevacor: In a 24-month carcinogenicity study in rats, there was a positive dose response relationship for hepatocellular carcinogenicity in males at drug exposures between 2-7 times that of human exposure at 80 mg/day (doses in rats were 5, 30 and 180 mg/kg/day).
Pravachol: Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year study in rats fed pravastatin at doses of 10, 30, or 100 mg/kg body weight, there was an increased incidence of hepatocellular carcinomas in males at the highest dose (p<0.01). These effects in rats were observed at approximately 12 times the human dose (HD) of 80 mg, based on body surface area mg/m2 and at approximately 4 times the human dose, based on AUC. In a 2-year study in mice fed pravastatin at doses of 250 and 500 mg/kg/day, there was an increased incidence of hepatocellular carcinomas in males and females at both 250 and 500 mg/kg/day (p<0.0001). At these doses, lung adenomas in females were increased (p=0.013). These effects in mice were observed at approximately 15 times (250 mg/kg/day) and 23 times (500 mg/kg/day) the human dose of 80 mg, based on AUC. In another 2-year study in mice with doses up to 100 mg/kg/day (producing drug exposures approximately 2 times the human dose of 80 mg, based on AUC), there were no drug-induced tumors. No evidence of mutagenicity was observed in vitro, with or without rat-liver metabolic activation, in the following studies: microbial mutagen tests, using mutant strains of Salmonella typhimurium or Escherichia coli ; a forward mutation assay in L5178Y TK +/- mouse lymphoma cells; a chromosomal aberration test in hamster cells; and a gene conversion assay using Saccharomyces cerevisiae. In addition, there was no evidence of mutagenicity in either a dominant lethal test in mice or a micronucleus test in mice.
Zocor: In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and midand high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day. In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC). In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC). A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other HMG-CoA reductase inhibitors. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose. No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in ZOCOR® (simvastatin) 9556649 14 an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
Crestor: (Jan 2006) In a 104-week carcinogenicity study in rats at dose levels of 2, 20, 60, or 80 mg/kg/day by oral gavage, the incidence of uterine stromal polyps was significantly increased in females at 80 mg/kg/day at systemic exposure 20 times the human exposure at 40 mg/day based on AUC. Increased incidence of polyps was not seen at lower doses. In a 107-week carcinogenicity study in mice given 10, 60, 200 mg/kg/day by oral gavage, an increased incidence of hepatocellular adenoma/carcinoma was observed at 200 mg/kg/day at systemic exposures 20 times human exposure at 40 mg/day based on AUC. An increased incidence of hepatocellular tumors was not seen at lower doses. Rosuvastatin was not mutagenic or clastogenic with or without me
Effect of Different Antilipidemic Agents and Diets on Mortality
A Systematic Review
Marco Studer, MD; Matthias Briel, MD; Bernd Leimenstoll, MD; Tracy R. Glass, MSc; Heiner C. Bucher, MD, MPH
Arch Intern Med. 2005;165:725-730.
Background Guidelines for the prevention and treatment of hyperlipidemia are often based on trials using combined clinical end points. Mortality data are the most reliable data to assess efficacy of interventions. We aimed to assess efficacy and safety of different lipid-lowering interventions based on mortality data.
Methods We conducted a systematic search of randomized controlled trials published up to June 2003, comparing any lipid-lowering intervention with placebo or usual diet with respect to mortality. Outcome measures were mortality from all, cardiac, and noncardiovascular causes.
Results A total of 97 studies met eligibility criteria, with 137 140 individuals in intervention and 138 976 individuals in control groups. Compared with control groups, risk ratios for overall mortality were 0.87 for statins (95% confidence interval [CI], 0.81-0.94), 1.00 for fibrates (95% CI, 0.91-1.11), 0.84 for resins (95% CI, 0.66-1.08), 0.96 for niacin (95% CI, 0.86-1.08), 0.77 for n-3 fatty acids (95% CI, 0.63-0.94), and 0.97 for diet (95% CI, 0.91-1.04). Compared with control groups, risk ratios for cardiac mortality indicated benefit from statins (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90). Risk ratios for noncardiovascular mortality of any intervention indicated no association when compared with control groups, with the exception of fibrates (risk ratio, 1.13; 95% CI, 1.01-1.27).
Conclusions Statins and n-3 fatty acids are the most favorable lipid-lowering interventions with reduced risks of overall and cardiac mortality. Any potential reduction in cardiac mortality from fibrates is offset by an increased risk of death from noncardiovascular causes.
Author Affiliations: Basel Institute for Clinical Epidemiology (Drs Studer, Briel, and Bucher and Ms Glass) and Department of Internal Medicine (Drs Studer and Leimenstoll), University Hospital Basel, Basel, Switzerland. (http://archinte.ama-assn.org/cgi/content/abstract/165/7/725)
An article on 2/19/8 from Wall Street Journal begins: COGNITIVE SIDE EFFECTS like memory loss and fuzzy thinking aren't listed on the patient information sheet for Lipitor, the popular cholesterol-lowering drug. But some doctors are voicing concerns that in a small portion of patients, statins like Lipitor may be helping hearts but hurting minds.
"This drug makes women stupid," Orli Etingin, vice chairman of medicine at New York Presbyterian Hospital, declared at a recent luncheon discussion sponsored by Project A.L.S. to raise awareness of gender issues and the brain. Dr. Etingin, who is also founder and director of the Iris Cantor Women's Health Center in New York, told of a typical patient in her 40s, unable to concentrate or recall words. Tests found nothing amiss, but when the woman stopped taking Lipitor, the symptoms vanished. When she resumed taking Lipitor, they returned.
"I've seen this in maybe two dozen patients," Dr. Etingin said later, adding that they did better on other statins. "This is just observational, of course. We really need more studies, particularly on cognitive effects and women."
Comments from visitors:
I was prescribed Mevacor about 20 years ago and became so incapacitated with muscle pain I had to seek medical attention. I was taken off the Mevacor and put on another, I can't remember which at this time, but over 20 years, I have been prescribed every statin available, the last was Crestor, which I took for 3 days and then had a heart attack. Before that, however, I was prescribed Tricor and my kidneys stopped after the 3rd dose and I became extremely ill. Then came the Crestor and the heart attack. For twenty years I have suffered from these muscular pains and when I expressed thoughts that they came from the cholesteral drug I was taking, they just gave me another. After my heart surgery and diagnosis of LAD, my surgeon, Dr. Rosenthal, told me to never take statins again; however, my cardiologist wanted me to try again and I refused and left the office no longer his patient. It has been two years since I have taken a cholesteral lowering drug and my cholesteral is now the lowest it has been since I first began statin therapy. (4/2/06)
My husband died last August 2005 of advanced liver cancer (hepatocellular carcinoma). He tested negative for hepatitis and cirrhosis as the common causes of liver cancer. Nothing ever was said about the lovastatin (mevacor) that he was on since 2003 when he had a mild heart attack. A friend (non-M.D.)mentioned the statin probably caused the cancer. Now, reading your research study results about mevacor and seeing the exact cancer that my husband had, I am wondering if it WAS the mevacor that caused the HCC. WHY was he not more closely monitored? I assume he wasn't since, by the time it was accidentally discovered, his cancer was too advanced to do anything. What can we do as laymen to protect ourselves if our physicians are not protecting us? His cardiologist, by the way, attended him even after his cancer was diagnosed and did not stop his medications. His primary doctor prescribed pain killers for 3 months for his pain and did not order any tests. Another doctor (when his primary was not available) ordered the CT-scan and that's when his cancer was discovered. He died 3 months later. We are with Kaiser - however, is the problem still there regardless of whether you are with an HMO or not? I really would like to know what our options are; what we can do, if anything. (5/5/06)
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If the authors contact me, I'll gladly remove it but I can simply link to it. Perhaps the intentions were good in the beginning, but the disease misunderstood, and the outcome terrible, all the while the corporate fat cats lined their pockets at the expense of peoples' arteries. To me, that is more morbid and disturbing than a horror movie but I am sure plenty of people will come to the aid of the statin camp. The next post I have will be even more mind boggling.
"Cancer, Longevity and Statins
Do statins cause cancer or affect longevity?
Editor's note: The following are a sample of results of a search on the safety of statins (Cholesterol lowering drugs; e.g. Lipitor, Mevacor, Pravachol, Zocor).
It appears that:
1. there is a danger that statins cause cancer in humans
2. death rates in the population have not been reduced as a result of statin use
3. prescribing sheets show that statins cause liver cancer in animals.
Cancer: Source - Journal of the American Medical Association (JAMA) January 1996 The following is an extract.
Carcinogenicity of lipid-lowering drugs.
Newman TB, Hulley SB.
Department of Laboratory Medicine, School of Medicine, University of California, San Francisco, USA.
OBJECTIVE--To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs. DATA SOURCES--Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts. STUDY SAMPLE--We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans. DATA SYNTHESIS--All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up.
CONCLUSIONS--Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.
Death Rate. Source: http://www.drugintel.com/drugs/statins/statins_critical_review.htm - This link was taken down.
Besides cancer, the other side effects of statins listed were incomplete, and should have included constipation, myalgia, myopathy, polyneuropathy, liver and kidney damage, congestive heart failure and amnesia. Side-effects are usually said to affect 2-6% of patients. In fact, a recent meta-analysis noted side-effects in 20% of patients above the placebo rate (65% vs. 45%), and no change whatever in the all-cause death rate for atorvastatin (Lipitor). [8] The PROSPER trial on pravastatin (Pravachol) showed no change in the all-cause death rate, and increased cancer and stroke rates. [9] Statins are commonly used at a dose to lower TC to <160 mg/dL, a level noted in the report of a NHLBI conference to be associated with higher cancer rates.[10]
Footnotes:
[8] Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of Atorvastatin Derived from Analysis of 44 Completed Trials in 9,416 Patients. Am J Cardiol 2003;92:670-6.
[9] Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360(9346):1623-30.
[10] Jacobs D, Blackburn H, Higgins M et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation 1992:86:1046-60.
Death Rate: Source: Archives of Internal Medicine Vol. 153 No. 9, May 10, 1993 Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data http://archinte.ama-assn.org/cgi/content/abstract/153/9/1065
Conclusion: Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population.
The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years. The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above. [Ed: - low cholesterol = higher non-chd mortality; high cholesterol = lower; CHD = Coronary Heart Disease]
Prescribing sheets published by manufacturers of statin drugs (Oct 2005): [ALL of them mentioned liver cancer as a side effect]
Lipitor: In a 2-year carcinogenicity study in rats at dose levels of 10, 30, and 100 mg/kg/day, 2 rare tumors were found in muscle in high-dose females: in one, there was a rhabdomyosarcoma and, in another, there was a fibrosarcoma. This dose represents a plasma AUC (0-24) value of approximately 16 times the mean human plasma drug exposure after an 80 mg oral dose. A 2-year carcinogenicity study in mice given 100, 200, or 400 mg/kg/day resulted in a significant increase in liver adenomas in high-dose males and liver carcinomas in highdose females. These findings occurred at plasma AUC (0-24) values of approximately 6 times the mean human plasma drug exposure after an 80 mg oral dose.
Mevacor: In a 24-month carcinogenicity study in rats, there was a positive dose response relationship for hepatocellular carcinogenicity in males at drug exposures between 2-7 times that of human exposure at 80 mg/day (doses in rats were 5, 30 and 180 mg/kg/day).
Pravachol: Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year study in rats fed pravastatin at doses of 10, 30, or 100 mg/kg body weight, there was an increased incidence of hepatocellular carcinomas in males at the highest dose (p<0.01). These effects in rats were observed at approximately 12 times the human dose (HD) of 80 mg, based on body surface area mg/m2 and at approximately 4 times the human dose, based on AUC. In a 2-year study in mice fed pravastatin at doses of 250 and 500 mg/kg/day, there was an increased incidence of hepatocellular carcinomas in males and females at both 250 and 500 mg/kg/day (p<0.0001). At these doses, lung adenomas in females were increased (p=0.013). These effects in mice were observed at approximately 15 times (250 mg/kg/day) and 23 times (500 mg/kg/day) the human dose of 80 mg, based on AUC. In another 2-year study in mice with doses up to 100 mg/kg/day (producing drug exposures approximately 2 times the human dose of 80 mg, based on AUC), there were no drug-induced tumors. No evidence of mutagenicity was observed in vitro, with or without rat-liver metabolic activation, in the following studies: microbial mutagen tests, using mutant strains of Salmonella typhimurium or Escherichia coli ; a forward mutation assay in L5178Y TK +/- mouse lymphoma cells; a chromosomal aberration test in hamster cells; and a gene conversion assay using Saccharomyces cerevisiae. In addition, there was no evidence of mutagenicity in either a dominant lethal test in mice or a micronucleus test in mice.
Zocor: In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and midand high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day. In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC). In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC). A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other HMG-CoA reductase inhibitors. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose. No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in ZOCOR® (simvastatin) 9556649 14 an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
Crestor: (Jan 2006) In a 104-week carcinogenicity study in rats at dose levels of 2, 20, 60, or 80 mg/kg/day by oral gavage, the incidence of uterine stromal polyps was significantly increased in females at 80 mg/kg/day at systemic exposure 20 times the human exposure at 40 mg/day based on AUC. Increased incidence of polyps was not seen at lower doses. In a 107-week carcinogenicity study in mice given 10, 60, 200 mg/kg/day by oral gavage, an increased incidence of hepatocellular adenoma/carcinoma was observed at 200 mg/kg/day at systemic exposures 20 times human exposure at 40 mg/day based on AUC. An increased incidence of hepatocellular tumors was not seen at lower doses. Rosuvastatin was not mutagenic or clastogenic with or without me
Effect of Different Antilipidemic Agents and Diets on Mortality
A Systematic Review
Marco Studer, MD; Matthias Briel, MD; Bernd Leimenstoll, MD; Tracy R. Glass, MSc; Heiner C. Bucher, MD, MPH
Arch Intern Med. 2005;165:725-730.
Background Guidelines for the prevention and treatment of hyperlipidemia are often based on trials using combined clinical end points. Mortality data are the most reliable data to assess efficacy of interventions. We aimed to assess efficacy and safety of different lipid-lowering interventions based on mortality data.
Methods We conducted a systematic search of randomized controlled trials published up to June 2003, comparing any lipid-lowering intervention with placebo or usual diet with respect to mortality. Outcome measures were mortality from all, cardiac, and noncardiovascular causes.
Results A total of 97 studies met eligibility criteria, with 137 140 individuals in intervention and 138 976 individuals in control groups. Compared with control groups, risk ratios for overall mortality were 0.87 for statins (95% confidence interval [CI], 0.81-0.94), 1.00 for fibrates (95% CI, 0.91-1.11), 0.84 for resins (95% CI, 0.66-1.08), 0.96 for niacin (95% CI, 0.86-1.08), 0.77 for n-3 fatty acids (95% CI, 0.63-0.94), and 0.97 for diet (95% CI, 0.91-1.04). Compared with control groups, risk ratios for cardiac mortality indicated benefit from statins (0.78; 95% CI, 0.72-0.84), resins (0.70; 95% CI, 0.50-0.99) and n-3 fatty acids (0.68; 95% CI, 0.52-0.90). Risk ratios for noncardiovascular mortality of any intervention indicated no association when compared with control groups, with the exception of fibrates (risk ratio, 1.13; 95% CI, 1.01-1.27).
Conclusions Statins and n-3 fatty acids are the most favorable lipid-lowering interventions with reduced risks of overall and cardiac mortality. Any potential reduction in cardiac mortality from fibrates is offset by an increased risk of death from noncardiovascular causes.
Author Affiliations: Basel Institute for Clinical Epidemiology (Drs Studer, Briel, and Bucher and Ms Glass) and Department of Internal Medicine (Drs Studer and Leimenstoll), University Hospital Basel, Basel, Switzerland. (http://archinte.ama-assn.org/cgi/content/abstract/165/7/725)
An article on 2/19/8 from Wall Street Journal begins: COGNITIVE SIDE EFFECTS like memory loss and fuzzy thinking aren't listed on the patient information sheet for Lipitor, the popular cholesterol-lowering drug. But some doctors are voicing concerns that in a small portion of patients, statins like Lipitor may be helping hearts but hurting minds.
"This drug makes women stupid," Orli Etingin, vice chairman of medicine at New York Presbyterian Hospital, declared at a recent luncheon discussion sponsored by Project A.L.S. to raise awareness of gender issues and the brain. Dr. Etingin, who is also founder and director of the Iris Cantor Women's Health Center in New York, told of a typical patient in her 40s, unable to concentrate or recall words. Tests found nothing amiss, but when the woman stopped taking Lipitor, the symptoms vanished. When she resumed taking Lipitor, they returned.
"I've seen this in maybe two dozen patients," Dr. Etingin said later, adding that they did better on other statins. "This is just observational, of course. We really need more studies, particularly on cognitive effects and women."
Comments from visitors:
I was prescribed Mevacor about 20 years ago and became so incapacitated with muscle pain I had to seek medical attention. I was taken off the Mevacor and put on another, I can't remember which at this time, but over 20 years, I have been prescribed every statin available, the last was Crestor, which I took for 3 days and then had a heart attack. Before that, however, I was prescribed Tricor and my kidneys stopped after the 3rd dose and I became extremely ill. Then came the Crestor and the heart attack. For twenty years I have suffered from these muscular pains and when I expressed thoughts that they came from the cholesteral drug I was taking, they just gave me another. After my heart surgery and diagnosis of LAD, my surgeon, Dr. Rosenthal, told me to never take statins again; however, my cardiologist wanted me to try again and I refused and left the office no longer his patient. It has been two years since I have taken a cholesteral lowering drug and my cholesteral is now the lowest it has been since I first began statin therapy. (4/2/06)
My husband died last August 2005 of advanced liver cancer (hepatocellular carcinoma). He tested negative for hepatitis and cirrhosis as the common causes of liver cancer. Nothing ever was said about the lovastatin (mevacor) that he was on since 2003 when he had a mild heart attack. A friend (non-M.D.)mentioned the statin probably caused the cancer. Now, reading your research study results about mevacor and seeing the exact cancer that my husband had, I am wondering if it WAS the mevacor that caused the HCC. WHY was he not more closely monitored? I assume he wasn't since, by the time it was accidentally discovered, his cancer was too advanced to do anything. What can we do as laymen to protect ourselves if our physicians are not protecting us? His cardiologist, by the way, attended him even after his cancer was diagnosed and did not stop his medications. His primary doctor prescribed pain killers for 3 months for his pain and did not order any tests. Another doctor (when his primary was not available) ordered the CT-scan and that's when his cancer was discovered. He died 3 months later. We are with Kaiser - however, is the problem still there regardless of whether you are with an HMO or not? I really would like to know what our options are; what we can do, if anything. (5/5/06)
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Saturday, August 15, 2009
Get your vitamins?
Of course get your vitamins.
As I get off of work, which currently preoccupies me with the prevention and treatment of diabetes mellitus naturally, I still find that we could all benefit from nutritional information.
From the angle I work, I contribute the fact that we are basically engines that require carbon fuel, water soluble elements, water, a little bit of very specific oils, a tiny bit of oil soluble elements, and air to work. Our physiques are sophisticated carbon engines that require more than just liquid alkanes and oxygen for combustion. If our fuels are tainted, even just slightly, our systems corrode over time. Every mechanic knows this intuitively, and all doctors should find this common sense too. Yet, they blindly ignore this and go on stubbornly as the face of youth fools them into thinking that old age will provide the same biological resilience as youth. Of course it won't. Not even in the best care will our carriage last much past 100 years old due to a "self-destruct" clock called "telomere." So I encourage all my associates and peers to look into healthy diets and augmenting their regimens with vitamins, minerals, amino acids, and herbal components.
You may or may not get to the century club, but you should get to whatever age you will be in grand and robust health and the fullness of life. To that end, you as a person who values this right should fight all effort to imprison you.
As I get off of work, which currently preoccupies me with the prevention and treatment of diabetes mellitus naturally, I still find that we could all benefit from nutritional information.
From the angle I work, I contribute the fact that we are basically engines that require carbon fuel, water soluble elements, water, a little bit of very specific oils, a tiny bit of oil soluble elements, and air to work. Our physiques are sophisticated carbon engines that require more than just liquid alkanes and oxygen for combustion. If our fuels are tainted, even just slightly, our systems corrode over time. Every mechanic knows this intuitively, and all doctors should find this common sense too. Yet, they blindly ignore this and go on stubbornly as the face of youth fools them into thinking that old age will provide the same biological resilience as youth. Of course it won't. Not even in the best care will our carriage last much past 100 years old due to a "self-destruct" clock called "telomere." So I encourage all my associates and peers to look into healthy diets and augmenting their regimens with vitamins, minerals, amino acids, and herbal components.
You may or may not get to the century club, but you should get to whatever age you will be in grand and robust health and the fullness of life. To that end, you as a person who values this right should fight all effort to imprison you.
Monday, August 10, 2009
Before you reach for that synthetic drug:
Remember that there are those who are sincerely interested in your well-being and would have you maintain your own health in your own hands, at your own control. That is my point and I don't really have any other message to send. Mine is that you can defeat major illness simply and naturally given knowledge revealed by science and the God given pharmacy of nature.
After all, every single synthetic drug owes its existence to Man making a discovery of nature. While I resist entering into political arguments and forays, one fatal chamber of humanity, I do encourage those who may be feeling unwell or who are sick to deeply investigate natural health regimens. Afterall, they are no different than pharmaceuticals. Pharmaceuticals are simply compounds or variations on what is in nature. Pharma Media has lead the majority to believe that pills are different from what is found in Nature.
The Deception uncovered is that everything is molecular in nature, and that a psychological trick has been played upon the public to believe that something that isn't in a pill isn't a molecule. Everything is a molecule. Our entire basis of existence and experience, regardless of whether it is sublime or foul is molecular.
The unfortunate fact is that there are charlatans, there are quacks, there are selfish entrepreneurs with bizarre distraction tactics. You will have to be diligent to see what is true and what is false to maintain your health without paying a Capitalist Cabal massive amounts of your hard earned money to stay well. That is my singular point - that you shouldn't have to make capitalists rich to stay well, because there are gifts of nature and evolution that will do you as well, and if that isn't a noble cause, I don't know what is.
After all, every single synthetic drug owes its existence to Man making a discovery of nature. While I resist entering into political arguments and forays, one fatal chamber of humanity, I do encourage those who may be feeling unwell or who are sick to deeply investigate natural health regimens. Afterall, they are no different than pharmaceuticals. Pharmaceuticals are simply compounds or variations on what is in nature. Pharma Media has lead the majority to believe that pills are different from what is found in Nature.
The Deception uncovered is that everything is molecular in nature, and that a psychological trick has been played upon the public to believe that something that isn't in a pill isn't a molecule. Everything is a molecule. Our entire basis of existence and experience, regardless of whether it is sublime or foul is molecular.
The unfortunate fact is that there are charlatans, there are quacks, there are selfish entrepreneurs with bizarre distraction tactics. You will have to be diligent to see what is true and what is false to maintain your health without paying a Capitalist Cabal massive amounts of your hard earned money to stay well. That is my singular point - that you shouldn't have to make capitalists rich to stay well, because there are gifts of nature and evolution that will do you as well, and if that isn't a noble cause, I don't know what is.
Monday, July 6, 2009
Vitamin C and Thrombosis
It is well known that vWf (von Willebrand factor) is essential for platelet aggregation in clotting. Those individuals deficient in it are somewhat hemophiliac.
It is also known the vWf is exposed and present at sites of endothelial (inner most layer of cells of artery) injury, at which platelets are attracted like iron filings to a magnet. This begins the cascade of thrombosis which is responsible for end-stage ischemic events. This is true whether there is or isn't a large plaque.
It is best not to have a plaque, as this can be a chronic homing beacon for trouble, but it must be remembered that the biochemical cascade is not cholesterol causing a jam in the lumen of the artery (that never happens), but a blood clot.
This may happen with or without a plaque bursting, although plaque burst definitely will expose the subendothelial vWf stuck to collagen that makes platelets stick.
PGI2 inhibits this platelet adhesion extremely effectively. PGI2 is prostacyclin.
Administering supranormal levels of ascorbic acid greatly enhances the levels of prostacyclin production into the bloodstream.
It is also known the vWf is exposed and present at sites of endothelial (inner most layer of cells of artery) injury, at which platelets are attracted like iron filings to a magnet. This begins the cascade of thrombosis which is responsible for end-stage ischemic events. This is true whether there is or isn't a large plaque.
It is best not to have a plaque, as this can be a chronic homing beacon for trouble, but it must be remembered that the biochemical cascade is not cholesterol causing a jam in the lumen of the artery (that never happens), but a blood clot.
This may happen with or without a plaque bursting, although plaque burst definitely will expose the subendothelial vWf stuck to collagen that makes platelets stick.
PGI2 inhibits this platelet adhesion extremely effectively. PGI2 is prostacyclin.
Administering supranormal levels of ascorbic acid greatly enhances the levels of prostacyclin production into the bloodstream.
Sunday, June 21, 2009
The Th1->Th2 Switch in HIV-AIDS Is an Allergy Hypothesis
This Israeli group describes AIDS as the immune response switch to Th2, with overabundant IgE, which then disables Th1 cytotoxic responses.
1: Virus Genes. 2004 Apr;28(3):319-31.
HIV-1 induced AIDS is an allergy and the allergen is the Shed gp120--a review,
hypothesis, and implications.
Becker Y.
Department of Molecular Virology, Faculty of Medicine, The Hebrew University of
Jerusalem, P.O. Box 12272, Jerusalem 91120, Israel. becker@med.huji.ac.il
The possibility that the induction of T helper 2 (Th2) cytokine synthesis and the gradual increase in interleukin 4 (IL-4) and IgE levels during HIV-1 infection are an allergic response to HIV-1 proteins was raised in the author's previous article [Becker, Virus Genes 28, 1-4, 2004]. The present review extends this hypothesis by citing experimental reports which indicate that HIV-1 shed gp120 virions share a striking resemblance with the allergens that bind to IgE molecules bound to Fc epsilon receptor I-positive (Fc epsilon RI) cells (mast cells, basophils, monocytes, and dendritic cells, DC) and then induce them to release and synthesize the IL-4 cytokine. In the earlier review, it was established that the IL-4 cytokine is responsible for the following processes: IgE synthesis by B cells and the inhibition of antiviral IgG synthesis; the inactivation of T helper 1 (Th1) cells; and the inhibition of the antiviral cytotoxic T cell (CTL) response. The binding of the shed gp120 to B cell-bound immunoglobulin (Ig) depletes these cells. Moreover, it was reported that the viral regulatory proteins Tat and Vpr also stimulate IL-4 release from basophils. The mode of action used by HIV-1 gp120 in the induction of IL-4 [Becker, Virus Genes 28, 1-14, 2004] revealed that the viral protein contains a superantigen (SAg) domain that is capable of binding to the V(H)3 domain of IgE and Ig; namely, the shed gp120 protein act as endogenous and environmental allergens that
bind to IgE molecules, which are bound to the Fc epsilon RI receptors on hematopoietic cells. Based on these findings, it is hypothesized that gp120 is an allergen. Consequently, it can be inferred that the active replication of HIV-1 in infected individuals constantly exposes the immune system to an increase in the allergen content until the host immunity is eventually compromised. These finding suggest that HIV-1 engage in a two-pronged attack of the human immune system: it infects Th2 cells, macrophages, and DCs and then replicates at these venues; and the shed gp120 cells cause an allergy. This allergic condition consequently prevents the induction of Th1 cells, cytokine synthesis, and antiviral CTLs that are needed to clear the infecting virus and thus devitalizes the antivirals that are used to treat the virus infection. It was hypothesized [Becker, Virus Genus 28, 1-14, 2004] that the HIV-1 induced allergy can be treated with IL-4 inhibitors or immune response modifiers. A treatment that employs both antivirals and anti-allergen drugs may very well defeat the AIDS syndrome. Another implication of the present hypothesis is the need to improve the viral antigen used for vaccinating healthy individuals against HIV-1 infection. It is thus suggested harmful domains be eliminated from the gp120.
PMID: 15266113 [PubMed - indexed for MEDLINE]
If this is true, there are many things which dampen Th2 and augment Th1 naturally, such as L-theanine, zinc, selenium, and things like citrus:
1: Mediators Inflamm. 2008;2008:496467. Epub 2008 Nov 30.
Citrus/Cydonia comp. can restore the immunological balance in seasonal allergic
rhinitis-related immunological parameters in vitro.
Baars EW, Savelkoul HF.
Department of Healthcare and Nutrition, Louis Bolk Instituut, 3972 LA Driebergen,
The Netherlands. e.baars@louisbolk.nl
In two in vitro studies, we examined the immunological (pathways of the) effects of Citrus/Cydonia comp. from, respectively, a healthy and an allergic donor; peripheral blood mononuclear cells (PBMCs) were isolated out of peripheral blood and analyzed in vitro after polyclonal stimulation of T-cells. The differentiation capacity and the influence with regard to Th1 (IFN-gamma) and Th2 (IL-5) cells were examined. Citrus/Cydonia comp. has a selective effect on the differentiation of T-cells by producing relatively more IL-10 than IL-12. By that, it also seems to have an effect on the induction of regulatory (IL-10 producing) T-cell subsets. It is in vitro capable of neutralizing (to some extent) the changes, characteristic to allergic rhinitis, with regard to the maturation, differentiation, and activity of the immune system. Thus, Citrus/Cydonia comp. can potentially restore the disturbed immune state of rhinitis patients, which essentially could be sufficient to make allergic
symptoms disappear permanently.
PMCID: PMC2590663
PMID: 19079587 [PubMed - indexed for MEDLINE]
1: Med Hypotheses. 1999 Jul;53(1):6-16.
Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide
(NO) collectively protect against viruses, AIDS, autoimmunity, diabetes,
allergies, asthma, infectious diseases, atherosclerosis and cancer.
Sprietsma JE.
Bennekom, The Netherlands.
Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2(PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
PMID: 10499817 [PubMed - indexed for MEDLINE]
1: Virus Genes. 2004 Apr;28(3):319-31.
HIV-1 induced AIDS is an allergy and the allergen is the Shed gp120--a review,
hypothesis, and implications.
Becker Y.
Department of Molecular Virology, Faculty of Medicine, The Hebrew University of
Jerusalem, P.O. Box 12272, Jerusalem 91120, Israel. becker@med.huji.ac.il
The possibility that the induction of T helper 2 (Th2) cytokine synthesis and the gradual increase in interleukin 4 (IL-4) and IgE levels during HIV-1 infection are an allergic response to HIV-1 proteins was raised in the author's previous article [Becker, Virus Genes 28, 1-4, 2004]. The present review extends this hypothesis by citing experimental reports which indicate that HIV-1 shed gp120 virions share a striking resemblance with the allergens that bind to IgE molecules bound to Fc epsilon receptor I-positive (Fc epsilon RI) cells (mast cells, basophils, monocytes, and dendritic cells, DC) and then induce them to release and synthesize the IL-4 cytokine. In the earlier review, it was established that the IL-4 cytokine is responsible for the following processes: IgE synthesis by B cells and the inhibition of antiviral IgG synthesis; the inactivation of T helper 1 (Th1) cells; and the inhibition of the antiviral cytotoxic T cell (CTL) response. The binding of the shed gp120 to B cell-bound immunoglobulin (Ig) depletes these cells. Moreover, it was reported that the viral regulatory proteins Tat and Vpr also stimulate IL-4 release from basophils. The mode of action used by HIV-1 gp120 in the induction of IL-4 [Becker, Virus Genes 28, 1-14, 2004] revealed that the viral protein contains a superantigen (SAg) domain that is capable of binding to the V(H)3 domain of IgE and Ig; namely, the shed gp120 protein act as endogenous and environmental allergens that
bind to IgE molecules, which are bound to the Fc epsilon RI receptors on hematopoietic cells. Based on these findings, it is hypothesized that gp120 is an allergen. Consequently, it can be inferred that the active replication of HIV-1 in infected individuals constantly exposes the immune system to an increase in the allergen content until the host immunity is eventually compromised. These finding suggest that HIV-1 engage in a two-pronged attack of the human immune system: it infects Th2 cells, macrophages, and DCs and then replicates at these venues; and the shed gp120 cells cause an allergy. This allergic condition consequently prevents the induction of Th1 cells, cytokine synthesis, and antiviral CTLs that are needed to clear the infecting virus and thus devitalizes the antivirals that are used to treat the virus infection. It was hypothesized [Becker, Virus Genus 28, 1-14, 2004] that the HIV-1 induced allergy can be treated with IL-4 inhibitors or immune response modifiers. A treatment that employs both antivirals and anti-allergen drugs may very well defeat the AIDS syndrome. Another implication of the present hypothesis is the need to improve the viral antigen used for vaccinating healthy individuals against HIV-1 infection. It is thus suggested harmful domains be eliminated from the gp120.
PMID: 15266113 [PubMed - indexed for MEDLINE]
If this is true, there are many things which dampen Th2 and augment Th1 naturally, such as L-theanine, zinc, selenium, and things like citrus:
1: Mediators Inflamm. 2008;2008:496467. Epub 2008 Nov 30.
Citrus/Cydonia comp. can restore the immunological balance in seasonal allergic
rhinitis-related immunological parameters in vitro.
Baars EW, Savelkoul HF.
Department of Healthcare and Nutrition, Louis Bolk Instituut, 3972 LA Driebergen,
The Netherlands. e.baars@louisbolk.nl
In two in vitro studies, we examined the immunological (pathways of the) effects of Citrus/Cydonia comp. from, respectively, a healthy and an allergic donor; peripheral blood mononuclear cells (PBMCs) were isolated out of peripheral blood and analyzed in vitro after polyclonal stimulation of T-cells. The differentiation capacity and the influence with regard to Th1 (IFN-gamma) and Th2 (IL-5) cells were examined. Citrus/Cydonia comp. has a selective effect on the differentiation of T-cells by producing relatively more IL-10 than IL-12. By that, it also seems to have an effect on the induction of regulatory (IL-10 producing) T-cell subsets. It is in vitro capable of neutralizing (to some extent) the changes, characteristic to allergic rhinitis, with regard to the maturation, differentiation, and activity of the immune system. Thus, Citrus/Cydonia comp. can potentially restore the disturbed immune state of rhinitis patients, which essentially could be sufficient to make allergic
symptoms disappear permanently.
PMCID: PMC2590663
PMID: 19079587 [PubMed - indexed for MEDLINE]
1: Med Hypotheses. 1999 Jul;53(1):6-16.
Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide
(NO) collectively protect against viruses, AIDS, autoimmunity, diabetes,
allergies, asthma, infectious diseases, atherosclerosis and cancer.
Sprietsma JE.
Bennekom, The Netherlands.
Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2(PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
PMID: 10499817 [PubMed - indexed for MEDLINE]
The Tragedy of Trivializing Natural Medicine Combined with Ignorance in HIV-AIDS
I was at the Stanford 10 year reunion, and I had someone come up to me and ask if I was going to prescribe beet-root, olive, lemon, and garlic to them.
The answer is a resounding yes, but only in the proper preparation, dosing, and indication. The idea that a salad or glass of veggie juice is going to help you in severe disease is, of course, absurd. So no, I am not going to suggest you eat a salad to cure your disease, which in this case may be mental. It turns out that a trained biologist, not a politician, or a trust-fund daughter with no background in biology would be able to see that each one of those have anti-viral molecules within them. If you were to extract and concentrate these, you would have an effective anti-viral medication. It really is sad that wealth blinds people from the truth.
BEET ROOT:
1: Cancer Lett. 1996 Feb 27;100(1-2):211-4.
Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract.
Kapadia GJ, Tokuda H, Konoshima T, Nishino H.
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical
Sciences, Howard University, Washington, DC 20059, USA.
The in vitro inhibitory effect of Beta vulgaris (beet) root extract on Epstein-Barr virus early antigen (EBV-EA) induction using Raji cells revealed a high order of activity compared to capsanthin, cranberry, red onion skin and short and long red bell peppers. An in vivo anti-tumor promoting activity evaluation against the mice skin and lung bioassays also revealed a significant tumor inhibitory effect. The combined findings suggest that beetroot ingestion can be one of the useful means to prevent cancer.
OLIVE:
PMID: 8620443 [PubMed - indexed for MEDLINE]
1: FEBS Lett. 2007 Jun 12;581(14):2737-42. Epub 2007 May 21.
Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion
protein gp41.
Bao J, Zhang DW, Zhang JZ, Huang PL, Huang PL, Lee-Huang S.
Department of Chemistry, New York University, New York, NY 10003, USA.
Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.
LEMON:
PMID: 17537437 [PubMed - indexed for MEDLINE]
1: J Biol Chem. 2004 Sep 3;279(36):37349-59. Epub 2004 Jun 24.
Imperatorin inhibits HIV-1 replication through an Sp1-dependent pathway.
Sancho R, Márquez N, Gómez-Gonzalo M, Calzado MA, Bettoni G, Coiras MT, Alcamí J,
López-Cabrera M, Appendino G, Muñoz E.
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de
Córdoba, Facultad de Medicina, Avda. de Menendez Pidal s/n, 14004 Córdoba, Spain.
Coumarins and structurally related compounds have been recently shown to present anti-human immunodeficiency virus, type 1 (HIV-1) activity. Among them, the dietary furanocoumarin imperatorin is present in citrus fruits, in culinary herbs, and in some medicinal plants. In this study we report that imperatorin inhibits either vesicular stomatitis virus-pseudotyped or gp160-enveloped recombinant HIV-1 infection in several T cell lines and in HeLa cells. These recombinant viruses express luciferase as a marker of viral replication. Imperatorin did not inhibit the reverse transcription nor the integration steps in the viral cell cycle. Using several 5' long terminal repeat-HIV-1 constructs where critical response elements were either deleted or mutated, we found that the transcription factor Sp1 is critical for the inhibitory activity of imperatorin induced by both phorbol 12-myristate 13-acetate and HIV-1 Tat. Moreover in transient transfections imperatorin specifically inhibited phorbol 12-myristate 13-acetate-induced transcriptional activity of the Gal4-Sp1 fusion protein. Since Sp1 is also implicated in cell cycle progression we further studied the effect of imperatorin on cyclin D1 gene transcription and protein expression and in HeLa cell cycle progression. W e found that imperatorin strongly inhibited cyclin D1 expression and arrested the cells at the G(1) phase of the cell cycle. These results highlight the potential of Sp1 transcription factor as a target for natural anti-HIV-1 compounds such as furanocoumarins that might have a potential therapeutic role in the management of AIDS.
GARLIC:
PMID: 15218031 [PubMed - indexed for MEDLINE]
1: Vestn Ross Akad Med Nauk. 1992;(11-12):6-10.
[The ajoene blockade of integrin-dependent processes in an HIV-infected cell
system]
[Article in ]
Tatarintsev AV, Vrzhets PV, Ershov DE, Shchegolev AA, Turgiev AS, Karamov EV,
Kornilaeva GV, Makarova TV, Fedorov NA, Varfolomeev SD.
Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, isolated from extracts of garlic (Allium sativum) has been previously shown to inhibit platelet aggregation by inactivating allosterically the platelet integrin, GP IIb/IIIa. The structural and functional similarity of integrins led the authors to suggest that ajoene may also inhibit adhesive interactions and fusion of leukocytes. Synthetic stereoisomers of ajoene synthesized by the authors exhibited equal antiaggregatory activities (IC100 approximately 50 microM for platelets; IC100 approximately 10 microM for fMLP-stimulated neutrophils). Racemic ajoene inhibited the fusion of H9 cells with HIV-infected H9:RF cells (IC50 approximately 45 microM; 16 h of incubation) and also exhibited a degree of antiviral activity (IC50 approximately 5 microM as assessed by inhibition of HIV-1/CEM/Lav 1 Bru replication in CEM13 cells; m. o. i. 0.1; 72 h). A
considerable increase in the latter became evident when the compound was administered in aliquots of 50 microM per 12 h of incubation (inhibition by 30%; total concentration 0.25 microM; 72 h).(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1284227 [PubMed - indexed for MEDLINE]
It's proof that an ivy league education doesn't do away with bias, bigotry, and superiority complexes that can blind you to the truth. When there is a real, good, affordable cure, then maybe you can ridicule these sources of medicine, which were the origins of modern medicine anyways. Until then, leave the research alone and stick to whatever you took classes for.
The answer is a resounding yes, but only in the proper preparation, dosing, and indication. The idea that a salad or glass of veggie juice is going to help you in severe disease is, of course, absurd. So no, I am not going to suggest you eat a salad to cure your disease, which in this case may be mental. It turns out that a trained biologist, not a politician, or a trust-fund daughter with no background in biology would be able to see that each one of those have anti-viral molecules within them. If you were to extract and concentrate these, you would have an effective anti-viral medication. It really is sad that wealth blinds people from the truth.
BEET ROOT:
1: Cancer Lett. 1996 Feb 27;100(1-2):211-4.
Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract.
Kapadia GJ, Tokuda H, Konoshima T, Nishino H.
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical
Sciences, Howard University, Washington, DC 20059, USA.
The in vitro inhibitory effect of Beta vulgaris (beet) root extract on Epstein-Barr virus early antigen (EBV-EA) induction using Raji cells revealed a high order of activity compared to capsanthin, cranberry, red onion skin and short and long red bell peppers. An in vivo anti-tumor promoting activity evaluation against the mice skin and lung bioassays also revealed a significant tumor inhibitory effect. The combined findings suggest that beetroot ingestion can be one of the useful means to prevent cancer.
OLIVE:
PMID: 8620443 [PubMed - indexed for MEDLINE]
1: FEBS Lett. 2007 Jun 12;581(14):2737-42. Epub 2007 May 21.
Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion
protein gp41.
Bao J, Zhang DW, Zhang JZ, Huang PL, Huang PL, Lee-Huang S.
Department of Chemistry, New York University, New York, NY 10003, USA.
Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.
LEMON:
PMID: 17537437 [PubMed - indexed for MEDLINE]
1: J Biol Chem. 2004 Sep 3;279(36):37349-59. Epub 2004 Jun 24.
Imperatorin inhibits HIV-1 replication through an Sp1-dependent pathway.
Sancho R, Márquez N, Gómez-Gonzalo M, Calzado MA, Bettoni G, Coiras MT, Alcamí J,
López-Cabrera M, Appendino G, Muñoz E.
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de
Córdoba, Facultad de Medicina, Avda. de Menendez Pidal s/n, 14004 Córdoba, Spain.
Coumarins and structurally related compounds have been recently shown to present anti-human immunodeficiency virus, type 1 (HIV-1) activity. Among them, the dietary furanocoumarin imperatorin is present in citrus fruits, in culinary herbs, and in some medicinal plants. In this study we report that imperatorin inhibits either vesicular stomatitis virus-pseudotyped or gp160-enveloped recombinant HIV-1 infection in several T cell lines and in HeLa cells. These recombinant viruses express luciferase as a marker of viral replication. Imperatorin did not inhibit the reverse transcription nor the integration steps in the viral cell cycle. Using several 5' long terminal repeat-HIV-1 constructs where critical response elements were either deleted or mutated, we found that the transcription factor Sp1 is critical for the inhibitory activity of imperatorin induced by both phorbol 12-myristate 13-acetate and HIV-1 Tat. Moreover in transient transfections imperatorin specifically inhibited phorbol 12-myristate 13-acetate-induced transcriptional activity of the Gal4-Sp1 fusion protein. Since Sp1 is also implicated in cell cycle progression we further studied the effect of imperatorin on cyclin D1 gene transcription and protein expression and in HeLa cell cycle progression. W e found that imperatorin strongly inhibited cyclin D1 expression and arrested the cells at the G(1) phase of the cell cycle. These results highlight the potential of Sp1 transcription factor as a target for natural anti-HIV-1 compounds such as furanocoumarins that might have a potential therapeutic role in the management of AIDS.
GARLIC:
PMID: 15218031 [PubMed - indexed for MEDLINE]
1: Vestn Ross Akad Med Nauk. 1992;(11-12):6-10.
[The ajoene blockade of integrin-dependent processes in an HIV-infected cell
system]
[Article in ]
Tatarintsev AV, Vrzhets PV, Ershov DE, Shchegolev AA, Turgiev AS, Karamov EV,
Kornilaeva GV, Makarova TV, Fedorov NA, Varfolomeev SD.
Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, isolated from extracts of garlic (Allium sativum) has been previously shown to inhibit platelet aggregation by inactivating allosterically the platelet integrin, GP IIb/IIIa. The structural and functional similarity of integrins led the authors to suggest that ajoene may also inhibit adhesive interactions and fusion of leukocytes. Synthetic stereoisomers of ajoene synthesized by the authors exhibited equal antiaggregatory activities (IC100 approximately 50 microM for platelets; IC100 approximately 10 microM for fMLP-stimulated neutrophils). Racemic ajoene inhibited the fusion of H9 cells with HIV-infected H9:RF cells (IC50 approximately 45 microM; 16 h of incubation) and also exhibited a degree of antiviral activity (IC50 approximately 5 microM as assessed by inhibition of HIV-1/CEM/Lav 1 Bru replication in CEM13 cells; m. o. i. 0.1; 72 h). A
considerable increase in the latter became evident when the compound was administered in aliquots of 50 microM per 12 h of incubation (inhibition by 30%; total concentration 0.25 microM; 72 h).(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1284227 [PubMed - indexed for MEDLINE]
It's proof that an ivy league education doesn't do away with bias, bigotry, and superiority complexes that can blind you to the truth. When there is a real, good, affordable cure, then maybe you can ridicule these sources of medicine, which were the origins of modern medicine anyways. Until then, leave the research alone and stick to whatever you took classes for.
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