Saturday, August 27, 2016
On a personal level, suffer from being ostracized by family, friends, medical community, alienation, massive financial losses, and social isolation.
I am still mostly homebound through periods of being bedbound. I had to give up law school through worsening symptoms, in particular severe weakness and severe cognition dysfunction.
Through the health quest journey, I made new friends, who in spite of adversities caused by their ADRs, shine through, resilient, strong, sharing the common goal on this journey. They are an inspiring bunch!!
For those of you hit by Lariam, Fluoroquinolones and/or other pharmaceuticals, keep hope, keep informed, keep searching what works for you. Few are hit severely, aim for recovery.
Posts will resume on ADR-Central and Health Quest in between relapses.
Wednesday, June 6, 2012
from medications. All toxicities from medications,
in particular, Lariam and Fluoroquinolones antibiotics,
will cause damage to endothelial cells, oxidization,
oxidative stress, inflammation = diseases/illnesses.
Join and discuss your symptoms, medications, and
other less toxic models leading to reversal of toxicities.
Friday, April 13, 2012
Health Quest forum offers a platform upon which to
explore least toxic options for all those who suffered adverse drug reaction (all meds) - Most are unaware their health issues
could have been triggered by meds.
- includes fluoroquinolones and all antibiotics, lariam/mefloquine and vaccines.
All welcome to join.
Information is key to Prevention.
Leading causes of illnesses are medications, toxicities and infections.
Published studies show 6 out of 10 hospitalized die as a result of medications.
High percentage of published medical research are falsified.
The forum is an attempt at bringing all suffering from
various illnesses under one banner.
Health Quest focuses on prevention (as in recovery or preventing more damage), solution and options.
Informative - provides a springboard for support and HOPE.
Many suffered primary symptoms, and recovered, whilst, others, suffer long term chronic illness resulting from damage caused by antibiotics (and lariam/mefloquine) known to reactivate certain infectious pathogens, damage to mitochondria cascading in chronic inflammation leading to diseases, such as cardiovascular, metabolic syndromes, myopathies and other dysfunctions at cellular level.
Join and keep safe.
Monday, January 16, 2012
Please sign the petition and pass this on to your
disabled and chronically ill friends.
Over 36 died in Scotland recently due to cuts
and DWP incentives. Many more are expected
to die. The CULLING has begun.
The UK government's eugenic style of budgetary incentive
towards the chronically ill is obscene. Fight back!!
Tweet the House of Lords and sign the petition.
URGENT - ask people to sign Pat's Petition TODAY
Last week the government was defeated three times on Welfare Reform.
Tomorrow there will be another debate in the Lords - this time on DLA.
Our contacts in the House of Lords say Pat's Petition is being watched
because it is a grassroots petition. High numbers of signatures give them
evidence of the strength of feeling behind everyone's actions. This is exactly what they need.
Sue Marsh is calling for a pause to reflect on DLA legislation in the light of
the Spartacus Report. If you want to support campaigners on Tuesday please help to get people to sign Pat’s Petition TODAY.
Pat's Petition asks for the government to stop and review all the changes to benefits that are creating a perfect storm. Pat's Petition has now reached almost 20,000 in a very short time.
Whether you've been on a Hardest Hit march, tweeted about the Spartacus Report or written to a Lord, please share the link as widely as possible in the run up to the vote on DLA on Tuesday. Keep sharing it so that Lord Freud and others know how many there are of us, watching their every move.
is the link to the petition.
twitter at http://twitter.com/PatsPetition
See Pat's Petition on FaceBook
Wednesday, November 9, 2011
Listen to this well articulated manipulations of Big Pharma & FDA in allowing dangerous life threatening toxic drugs passed as "safe", inventing new diseases to fit Big Pharma's monopoly on health care, government health officials and medical professionals in collusion.
Lawlessness, anarchy, against the constitution, the FDA and Big Pharma ignore court orders!!
Monday, April 18, 2011
All welcome to join, in particular, those who suffered adverse reactions (ADRs) from all antibiotics, including fluoroquinolones, lariam/mefloquine and those who had vaccines shots shortly before/after taking the aforementioned, (and other medications).
The forum is an attempt at bringing all under one banner.
Health Quest focuses on prevention (as in recovery or preventing more damage), solution and options. Info and tips, and is a springboard for support and HOPE.
Although many of us suffered primary symptoms and recovered, others, suffered long term chronic illness resulting from damage caused by antibiotics (and lariam/mefloquine) known to reactivate certain infectious pathogens, damage to mitochondria cascading in chronic inflammation leading to diseases, such as cardiovascular, metabolic syndromes, myopathies and other dysfunctions at cellular level.
Friday, March 18, 2011
Friday, March 11, 2011
Clearly, prevention is paramount, secondly, look at other options of dealing with health issues, and thirdly, be responsible for your own health issues. Read up on the pharmacological content of prescribed meds, validity, the science, effective?, side effects and adverse reactions. Read about what other patients themselves experienced, over a period of time. Most who suffer ill health do not make the association with off the counter meds and/or prescribed meds. It takes longer than a few weeks or months, sometimes years for inflammation to progress.
Nuclear Receptors and the Regulation of Drug-Metabolizing Enzymes and Drug Transporters: Implications for Interindividual Variability in Response to Drugs
1. Bradley L. Urquhart, PhD
2. Rommel G. Tirona, PhD
3. Richard B. Kim, MD
From the Division of Clinical Pharmacology, Department of Medicine (Dr Urquhart, Dr Tirona, Dr Kim), and the Department of Physiology & Pharmacology (Dr Tirona), University of Western Ontario, London, Ontario, Canada.
1. Address for correspondence: Richard B. Kim, MD, Division of Clinical Pharmacology, London Health Sciences Centre—University Hospital, Room ALL-152, 339 Windermere Road, London, Ontario N6A 5A5, Canada; e-mail: firstname.lastname@example.org.
Erratic or unpredictable response to drugs remains a challenge of modern drug therapy. An important determinant of such interindividual differences in drug response is variability in the expression of drug-metabolizing enzymes and/or transporters at sites of absorption and/or tissue distribution. Variable drug-metabolizing enzyme and transporter expression can result in unpredictable exposure and tissue distribution of drugs and may manifest as adverse effects or therapeutic failure. In the past decade, important new insights have been made relating to the regulatory mechanisms governing the expression of drug-metabolizing enzymes and transporters by ligand-activated nuclear receptors. Specifically, there is compelling evidence to demonstrate that PXR, CAR, FXR, LXR, VDR, HNF4α, and AhR form a battery of nuclear receptors that regulate the expression of many important drug-metabolizing enzyme and transporters. In this review, the authors focus on clinically important drug-metabolizing enzymes such as CYP3A4, CYP2B6, CYP2C9, CYP2C19, UGT1A1, SULT2A1, and glutathione S-transferases and their regulation by nuclear receptors. They also review the nuclear receptor-mediated regulation of drug transporters such as MDR1, MRP2, MRP4, BSEP, BCRP, NTCP, OATP1B3, and OATP1A2. Finally, they outline how the drug development process has been affected by the current understanding of the involvement of nuclear receptors in the regulation of drug disposition genes. http://tinyurl.com/5t5qzcd
I was curious about comparative study for ADRs between Fqs and other antibiotics. Those who are suffering from ADRs, (NOT allergic reactions), from other antibiotics, take note. So yes, many of us, have/had ADRs from non FQs pre/post floxing!! Figures seem to vary, one other study show cephalosporins to be between 19-40%...
Abstract and Introduction
Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug-drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997). http://www.medscape.com/viewarticle/418295
For those who are still keen on taking antibiotics, read about the mitochondria cytoxicity, which means essentially, DNA damage. There are several articles posted on the forum about damage to mitochondria, worse offenders are: antibiotics (Fqs, macrolides, tetracyclines, clyndamicin, Rifamopin), anti-depressants and NSAIDs... This study is well designed and discusses glycation, cell death, lactic acidosis etc. http://aac.asm.org/cgi/reprint/AAC.00729-05v1.pdf
For those of us who are having problems with foods, vits & supps, and metabolozing drugs, read on...
It appears that minute dosage of anything is not being metabolized (for some of us), and reaches a level of toxicity. This can apply to some compounds in some type of foods. This partly explains the inability to metabolize, the aforementioned including environmental pollutants.
"Enzymes that metabolize xenobiotics have historically
been called drug-metabolizing enzymes, although they are
involved in the metabolism of many foreign chemicals to
which humans are exposed. Dietary differences among
species during the course of evolution could account for
the marked species variation in the complexity of the
Today, most xenobiotics to which humans are exposed
come from sources that include environmental pollution,
food additives, cosmetic products, agrochemicals, processed
foods, and drugs. In general, these are lipophilic
chemicals, that in the absence of metabolism would not be
efficiently eliminated, and thus would accumulate in the
body, resulting in toxicity. With very few exceptions, all
xenobiotics are subjected to one or multiple pathways that
constitute the phase 1 and phase 2 enzymatic systems. As
a general paradigm, metabolism serves to convert these
hydrophobic chemicals into derivatives that can easily be
eliminated through the urine or the bile."http://books.mcgraw-hill.com/medical/goodmanandgilman/pdfs/CHAPTER3.pdf
Sunday, February 20, 2011
The article mentions Hyaluronic Acid in cream form for joints pains.
In addition, since there is accumulation of uric acid in joints causing pains, it might be worth trying a diet low in purines:
Adverse antibiotic-induced eruptions associated with epstein barr virus infection and showing Kikuchi-Fujimoto disease-like histology.
Carlson JA, Perlmutter A, Tobin E, Richardson D, Rohwedder A.
Division of Dermatology, Department of Pathology, Albany Medical College, Albany, New York 12208, USA. email@example.com
The antibiotic-induced eruption of infectious mononucleosis is a well-known clinical phenomenon. Latent viral infection with herpesviridae (eg, human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV)) is suspected to play a role in the drug hypersensitivity syndrome. The cutaneous pathologic findings have not been reported in the former, and are infrequently reported in the latter entity. Herein, we describe the biopsy findings of a cefprozil-induced rash in infectious mononucleosis and a minocycline-associated drug hypersensitivity syndrome. Biopsy of these exanthematous eruptions revealed an acute vacuolar interface superficial and deep perivascular and interstitial lymphocytic dermatitis. CD8(+) lymphocytes predominated and were associated with non-neutrophilic nuclear (karyorrhectic) debris and numerous small CD68(+) and CD123(+) monocytes. These aforementioned features have been described in cutaneous lesions of Kikuchi-Fujimoto disease, an entity whose clinicopathologic findings overlap with both infectious mononucleosis and lupus erythematosus. Serologic evidence of active and chronic active EBV infection was found in both patients, respectively. No evidence of EBV or HHV6 was found in the cutaneous lesions. Plasmacytoid monocytes (CD68(+)/CD123(+) cells), which produce type I interferon, are believed to play a role in viral immunity by protecting other cells from viral infections and promoting survival of antigen-activated T cells. Their presence in these two putative examples of viral-drug immune dysregulation could be a clue to pathogenesis and represent a common cellular component of some adverse cutaneous drug eruptions.
Aside the well known side effects of FQs, other antibiotics also cause damage to tendons, CNS symptoms and so forth.
"adverse effects for various fluoroquinolones was 3-40%. By comparison, these same studies reported adverse event rates of 2-49% for trimethoprim-sulfamethoxazole, 6-35% for penicillins, 12-39% for cephalosporins, 19-23% for doxycycline, and approximately 39% for erythromycin.[10,11]"
Abstract and Introduction
Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug-drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997).
Fluoroquinolones are considered to be safe and well tolerated,[1-4] although there are some notable exceptions, for example, temafloxacin, trova-floxacin, and, more recently, grepafloxacin.[5-9] This is especially true when fluoroquinolones are compared with other commonly prescribed antimicrobials.[3, 4] A review of safety results from numerous controlled clinical trials revealed that, overall, the agents are not significantly different from -- and in some cases were superior to -- nonquinolone comparators or placebo in occurrence of adverse events.[10, 11] Overall rates of adverse effects and rates of drug discontinuation from premarketing clinical studies of fluoro-quinolones are summarized in Table 1. [2-4,6,7,10-44]
Fluoroquinolones are generally highly comparable with other classes of antibiotics in terms of overall frequency and severity of adverse effects, although specific adverse effects vary among drug classes. In comparative clinical studies, the overall frequency of adverse effects for various fluoroquinolones was 3-40%. By comparison, these same studies reported adverse event rates of 2-49% for trimethoprim-sulfamethoxazole, 6-35% for penicillins, 12-39% for cephalosporins, 19-23% for doxycycline, and approximately 39% for erythromycin.[10,11]
True rates of adverse effects are often extremely difficult to determine. Comparative clinical studies may report two types of adverse events: treatment-emergent and drug-related. Treatment-emergent adverse effects are reported by study participants during the study. These are frequently quite subjective and are often not related to the study drug(s). Therefore, adverse event rates associated with administration of placebo are often as high as those associated with active agents. Treatment-emergent event rates also reflect adverse effects that are drug related. Although these rates are often much higher than the frequency of true drug-related adverse effects, they are reported because of difficulty determining causality. Drug-related adverse effect rates, when available, are usually much more useful with regard to agents of different classes as well as to those of the same class. Adverse effect rates of fluoroquinolones summarized in Table 1 include those that were reported to be possibly or probably drug related.
Most adverse events caused by fluoroquinolones are comparable, although overall frequency and manifestation of certain adverse effects differ among agents ( Table 2 ).[4,10] Each fluoroquinolone tends to produce a characteristic profile of adverse effects; differences often are explained by structural features and related relationships of the class. The events are typically mild and usually resolve during continued treatment or with discontinuation of therapy, although early discontinuation for an event is unusual. Gastrointestinal effects (e.g., nausea, diarrhea) and central nervous system (CNS) effects (e.g., headache, dizziness) are most common. Toxic effects that are observed only in animal models or that have not been shown to be clinically relevant in humans include chondrotoxicity, reproductive and developmental toxicity, genotoxicity, and carcinogenicity.[2-4,10,11] Concerns regarding bone and joint toxicities in juvenile animal models thus far have precluded approval of fluoroquinolones for treatment of infections in children. However, more recent data indicate that the agents may be safe in this population, and this is being actively explored.
Read more: http://noquinolones.proboards.com/index.cgi?board=theories&action=display&thread=1813#ixzz1EWiceWCj
Tuesday, February 1, 2011
Tuesday, January 18, 2011
60 Minutes Exposes the Maker of the #1 Most Fatal Drug of 2009
From Dr Mercola's site:
Drug company whistle-blower Cheryl Eckard talks about her experience trying to fix problems at GlaxoSmithKline. Her discoveries about the dangerous practices of the company made her a key figure in a federal lawsuit.
...... Due to various production line failures, powerful medications were also getting mixed up. Potent and potentially dangerous drugs were literally ending up in the wrong bottles! The antidepressant Paxil was mixed into bottles of Avandia, a diabetes drug. And Avandia was found in packages of the over-the-counter antacid Tagamet. All in all, Eckard identified nine different mix-ups of various drugs. http://tinyurl.com/4dj8nfe
Tuesday, January 11, 2011
See other posts on Triphala, an Ayurvedic compound used for gentle detoxing, over a long period of time. It contains anti-oxidants compounds from three Asian fruits. The mix is anti bacterial, anti-viral, purifies the blood and organs, as well as aids the digestive system and bowel movement if taken at night. It also has various other beneficial properties as well as protection against radiation.
The article below discusses the radioprotective effects of Triphala:
The evaluation of the radioprotective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to [gamma]-radiation.
The effect of 0, 5, 6.25, 10, 12.5, 20, 25, 40, 50 and 80 mg/kg b. wt. of aqueous extract of triphala (an Ayurvedic herbal medicine) administrered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of [gamma]-radiation. Treatment of mice with different doses of triphala consecutively for five days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. The highest protection against GI (gastrointestinal) death was observed for 12.5 mg/kg triphala, where a highest number of survivors were reported up to 10 days post-irradiation. While 10 mg/kg triphala i.p. provided the best protection as evidenced by the highest number of survivors after 30 days post-irradiation in this group when compared with the other doses of triphala. Toxicity study showed that triphala was non-toxic up to a dose of 240 mg/kg, where no drug-induced mortality was observed. The [LD.sub.50] dose i.p. o f triphala was found to be 280 mg/kg b. wt. Our study demonstrates the ability of triphala as a good radioprotective agent and the optimum protective dose of triphala was 1/28 of its [LD.sub.50] dose.
Key words: Triphala, radiation, mice, survival, acute toxicity, radioprotection ra·di·o·pro·tec·tion
Protection against the harmful effects of radiation.
..... Click the link for more information., Terminalia chebula Retz., Phyllanthus emblica Linn. or Emblica officinalis Gaertn. and Terminalia bellerica (Gaertn.) Roxb.
Friday, January 7, 2011
A significant percentage of newly diagnosed patients are turning to safer modalities. Sadly, most die of side effects from toxic drugs and invasive tests rather than the primary cancer. Furthermore, many cancer patients develop new cancers caused by chemo, radiation and arsenal of unnecessary drugs.
Breaking News: Popular Cancer Drug Declared More Harmful Than Helpful
The FDA has said that the controversial drug Avastin should be phased out as a treatment for metastatic breast cancer. Recent studies show that its benefits are outweighed by dangerous side effects.
The announcement does not affect Avastin's status as a drug that can be prescribed for lung cancer, kidney cancer, colorectal cancer and brain cancer.
In 2008, the FDA granted Avastin accelerated approval for use to treat metastatic breast cancer. But studies have failed to show that patients getting Avastin lived longer than patients on standard chemotherapies.
According to CNN:
"Along with those disappointing findings, serious side effects became apparent in patients taking Avastin, including high blood pressure, internal bleeding, perforated internal organs, heart failure and heart attacks, and in some cases, even swelling of the brain."
Genentech, which makes Avastin, has a right to appeal the decision.
Folks, the best way of preventing breast cancer isn't a drug at all, and it's free! Sun exposure may be the single most effective means of reducing breast cancer, thanks to vitamin D, which forms in your body in reaction to sunlight. In a recent study, data collected over a decade from more than 67,000 women showed that women in sunny climes with high vitamin D levels were at a significantly reduced risk of breast cancer!
CNN December 16, 2010
Cancer Epidemiology, Biomarkers and Prevention December 2, 2010
Popular Breast Cancer Drug Proven More Harmful than Helpful
Avastin, which costs about $8,000 a month and is one of the best-selling cancer drugs in the world, is now being phased out in the US due to lack of effectiveness and dangerous side effects.
As reported by CNN, the FDA has deemed the drug to be more harmful than beneficial based on recent studies, and recommends phasing it out as a treatment for metastatic breast cancer.
The drug will still maintain its status as an approved therapy for lung-, kidney-, colorectal- and brain cancer, however.
The European Medicines Agency is also altering its recommendation, but rather than withdrawing approval entirely, Avastin will now only be prescribed in combination with the drug Paclitaxel for the treatment of breast cancer in the EU.
Thursday, December 23, 2010
Tuesday, December 21, 2010
By Michael C. Cohen, president of the Institute for Safe Medication Practices
The link between violence and prescription drugs has rarely been studied. However, a study published last week in the journal PLoS ONE identified 31 drugs that are disproportionally associated with reported cases of violence.
The study drew on reports of violence and aggression made to the Food and Drug Administration from 2004 through the third quarter of 2009. While far from definitive, these findings signal that more research is needed.
Leading the list in numbers of reports is the smoking cessation drug Chantix (varenicline).
Also associated with violence were psychoactive medications for depression (Prozac and Paxil), attention deficit disorder (Strattera), and sedative/hypnotic drugs.
The authors, Thomas J. Moore, a consulting senior scientist at the Institute for Safe Medication Practices, Joseph Glenmullen of Harvard Medical School, and Curt D. Furberg of Wake Forest University School of Medicine, selected cases from the ISMP QuarterWatch database, which is composed of computer extracts of all adverse drug event reports received by FDA.
A violent event was defined as any case report mentioning homicide, physical assault, physical abuse, homicidal ideation or violence-related symptom.
For the five-year study period, the authors identified 484 drugs that accounted for 780,169 serious adverse event reports of all kinds. This total included 1,937 (0.25 percent) cases that met the violence criteria.
Thirty-one drugs met study criteria for a disproportionate association with violence, accounting for 1,527 (79 percent) of the violence cases.
Included were 387 reports of actual homicide, 404 that were physical assaults, 223 cases with violence-related symptoms, and 896 homicidal ideation reports.
The prominence of Chantix was not a surprise. An association between that drug and serious psychiatric symptoms, including hostile behavior, was also a finding in a 2008 study by our group that looked at FDA adverse event reports in the fourth quarter of 2007. The authors of the present study had earlier linked Chantix to thoughts and acts of aggression/violence. The association also led FDA to require product label changes, including a boxed warning for the drug.
The authors conclude that their data "provide new evidence" that violent acts are "associated with a relatively small group of drugs" and that systematic studies "are needed to establish the incidence, confirm differences among drugs and identify additional common features."
Read more: http://www.philly.com/inquirer/magazine/20101220_Check_Up.html
Friday, December 17, 2010
Few studies discuss the balance between "moping" up excess free radicals and upsetting biochemistry balance of free radicals, or if taking long term anti oxidants therapy, how would the body's natural defense cope under physiological stress? Its role in preventing further oxidization, or halting/reversing inflammation process?
Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine
Mehar DARUKHSHAN Kalim email, Dipto Bhattacharyya email, Anindita Banerjee email and Sharmila Chattopadhyay email
BMC Complementary and Alternative Medicine 2010, 10:77doi:10.1186/1472-6882-10-77
Published: 16 December 2010
There is increasing recognition that many of today's diseases are due to the "oxidative stress" that results from an imbalance between the formation and neutralization of reactive molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can be removed with antioxidants. The main objective of the present study was to evaluate the antioxidant activity of plants routinely used in the Unani system of medicine. Several plants were screened for radical scavenging activity, and the ten that showed promising results were selected for further evaluation.
Methanol (50%) extracts were prepared from ten Unani plants, namely Cleome icosandra, Rosa damascena, Cyperus scariosus, Gardenia gummifera, Abies pindrow, Valeriana wallichii, Holarrhena antidysenterica, Anacyclus pyrethrum, Asphodelus tenuifolius and Cyperus scariosus, and were used to determine their total phenolic, flavonoid and ascorbic acid contents, in vitro scavenging of DPPH * , ABTS * +, NO, * OH, O2.- and ONOO, and capacity to prevent oxidative DNA damage. Cytotoxic activity was also determined against the U937 cell line.
IC50 values for scavenging DPPH * , ABTS * +, NO, * OH, O2.- and ONOO were in the ranges 0.007+/- 0.0001 - 2.006 +/- 0.002 mg/ml, 2.54 +/- 0.04 - 156.94 +/- 5.28 mug/ml, 152.23 +/- 3.51 - 286.59 +/- 3.89 mug/ml, 18.23 +/- 0.03 - 50.13 +/- 0.04 mug/ml, 28.85 +/- 0.23 - 537.87 +/- 93 mug/ml and 0.532 +/- 0.015 - 3.39 +/- 0.032 mg/ml, respectively. The total phenolic, flavonoid and ascorbic acid contents were in the ranges 62.89 +/- 0.43 -166.13 +/- 0.56 mg gallic acid equivalent (GAE)/g extract, 38.89 +/- 0.52 - 172.23 +/- 0.08 mg quercetin equivalent (QEE)/g extract and 0.14 +/- 0.09 - 0.98 +/- 0.21 mg AA/g extract. The activities of the different plant extracts against oxidative DNA damage were in the range 0.13-1.60 ug/ml. Of the ten selected plant extracts studied here, seven - C. icosandra, R. damascena, C. scariosus, G. gummifera, A. pindrow, V. wallichii and H. antidysenterica - showed moderate antioxidant activity. Finally, potentially significant oxidative DNA damage preventive activity and antioxidant activity were noted in three plant extracts: C. icosandra, R. damascena and C. scariosus. These three plant extracts showed no cytotoxic activity against U937 cells.
The 50% methanolic extracts obtained from different plant parts contained significant amounts of polyphenols with superior antioxidant activity as evidenced by the scavenging of DPPH * , ABTS * +, NO, * OH, O2.- and ONOO. C. icosandra, R. damascena and C. scariosus showed significant potential for preventing oxidative DNA damage and radical scavenging activity, and the G. gummifera, A. pindrow, V. wallichii, H. antidysenterica, A. pyrethrum, A. tenuifolius and O. mascula extracts showed moderate activity. The extracts of C. icosandra, R. damascena and C. scariosus showed no cytotoxicity against U937 cells. In conclusion, these routinely used Unani plants, especially C. icosandra, R. damascena and C. scariosus, which are reported to have significant activity against several human ailments, could be exploited as potential sources of natural antioxidants for plant-based pharmaceutical industries.
Thursday, December 16, 2010
other studies are showing similar benefits in slowing progression of heart failure and improves survival rates post myocardial infarct.
* Rabbani N, Alam, SS, Riaz S, et al. High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. Diabetologia. 2008 Dec 5.
Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response.
Katare R, Caporali A, Emanueli C, Madeddu P.
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Benfotiamine (BFT) is a transketolase activator that directs glucose to the pentose phosphate pathway. The present study investigated whether BFT improves the recovery after myocardial infarction (MI) and explored underlying mechanisms of protection. Non-diabetic and streptozotocin-induced type 1 diabetic mice were supplemented with BFT (70 mg/kg/day in drinking water) for 4 weeks and then subjected to MI or sham operation. Cardiac function was monitored by echocardiography. At two weeks post-MI, intra-ventricular pressure was measured by Millar tip-catheter and hearts were collected for biochemical, immunohistochemical and expressional analyses. No treatment effect was observed in sham-operated mice. Post-MI mortality was higher in diabetic mice and hemodynamic studies confirmed the worsening effect of diabetes on functional recovery. Furthermore, diabetic mice demonstrated increased cardiomyocyte apoptosis, reduced reparative angiogenesis, larger scars, enhanced oxidative stress, and blunted activation of the pro-survival VEGF receptor-2/Akt/Pim-1 signaling pathway. BFT improved post-MI survival, functional recovery and neovascularization and reduced cardiomyocyte apoptosis and neurohormonal activation in diabetic as well as in non-diabetic mice. In addition, BFT stimulated the activity of pentose phosphate pathway enzymes, leading to reduction of oxidative stress, phosphorylation/activation of VEGF receptor-2 and Akt and increased Pim-1, pBad and Bcl-2 levels. These effects were contrasted on silencing glucose-6-phosphate dehydrogenase, the key enzyme in pentose phosphate pathway, or inhibiting Akt. BFT benefits post-MI recovery through stimulation of pro-survival mechanisms and containment of neurohormonal response. These results may have implications for the treatment of myocardial ischemia.
Wednesday, December 15, 2010
13 Drugs on Latest FDA List for Safety Monitoring
July 2, 2010 — A watch list of 13 drugs based on potential signs of serious risks or new safety information collected by the Adverse Event Reporting System (AERS) of the US Food and Drug Administration (FDA) during the first quarter of 2010 has been released.
The FDA is studying all of the drugs to determine the need for any regulatory action.
A drug's appearance on the watch list does not mean the agency has determined that the drug poses the health risk in question. Physicians should not stop prescribing the drug, and patients should not stop taking it, according to the FDA.
The FDA is evaluating 2 antibiotics — azithromycin (Zithromax; Pfizer) and clarithromycin (Biaxin; Abbott) — to find out whether they are associated with liver failure. Suspicions about azithromycin and liver failure are not new. The label for the antibiotic states that adverse events discovered after the drug entered the marketplace — and for which a causal relationship may not be established — include "abnormal liver function including hepatitis and cholestatic jaundice, as well as rare cases of hepatic necrosis and hepatic failure, some of which have resulted in death." During clinical trials, cholestatic jaundice was a rarely reported adverse effect.
Postmarketing adverse events for clarithromycin have included infrequent cases of sometimes severe, but usually reversible, hepatic dysfunction, including cholestatic hepatitis, with or without jaundice. There also have been rare and fatal cases of hepatic failure "associated with serious underlying diseases and/or concomitant medications," according to the drug label. Cholestatic jaundice did not emerge as an adverse effect in clinical trials.
Two other antibiotics made it on the latest watch list. AERS turned up reports of pyloric stenosis linked to azithromycin extended release 2 g (Zmax; Pfizer) and pulmonary eosinophilia and eosinophilic pneumonia linked to daptomycin (Cubicin; Cubist Pharmaceuticals).
FDA Studying Anticoagulant to Determine Whether It Causes Blood Clots
Three other medications on the watch list are in the cardiovascular camp. The anticoagulant prasugrel (Effient; Eli Lilly), is being watched on account of thrombotic thrombocytopenic purpura — a rare and life-threatening disorder that causes clots to form in small blood vessels throughout the body. The drug's label warns that this disorder emerged as an adverse effect during clinical trials. Heartwire recently reported that researchers continue to debate whether the medication increases the risk for cancer.
Another drug, dronedarone (Multaq; Sanofi-Aventis), used to treat atrial fibrillation and atrial flutter, has come under surveillance because of reports of congestive heart failure. As reported by Heartwire, clinicians have considered dronedarone a safer alternative to amiodarone (Cordarone; Wyeth-Ayerst; Pacerone; Upsher-Smith) for patients with atrial fibrillation.
The third cardiovascular drug on the watch list is ranolazine (Ranexa; Gilead), prescribed for patients with angina. Here, the FDA is investigating reports of torsades de pointes — a ventricular tachycardia that can lead to sudden death.
Two medications prescribed for narcolepsy — modafinil (Provigil; Cephalon) and sodium oxybate (Xyrem; Jazz Pharmaceuticals) — are under study for a possible association with convulsions. Physicians prescribe modafinil to counteract excessive sleepiness caused by narcolepsy, sleep apnea, or shift work. Likewise, sodium oxybate reduces daytime sleepiness, as well as the number of cataplexy attacks suffered, in patients with narcolepsy.
Perhaps the most well-known product on the watch list is the blend of estrogens marketed as Premarin (Wyeth), used to treat symptoms of menopause. It landed on the list based on reports of angioedema.
Potential Signals of Serious Risks/New Safety Information Identified by AERS, First Quarter 2010 http://www.medscape.com/viewarticle/724545?sssdmh=dm1.624895&src=nldne&uac=128675HJ
Montelukast used to treat asthma has been linked to severe CNS reactions, including suicide ideation and self harm. http://www.leaderpost.com/news/Asthma+drug+linked+suicide+attempts+thoughts+self+harm/1768232/story.html
The article below, concerns inhaled corticosteroid and Diabetes Mellitus.
Inhaled Corticosteroid Use May Increase Risk for Diabetes Mellitus
Laurie Barclay, MD
December 15, 2010 — Inhaled corticosteroid use may increase the risk for diabetes mellitus, according to the results of a study reported in the November issue of the American Journal of Medicine.
"High doses of inhaled corticosteroids commonly used in patients with [chronic obstructive pulmonary disease (COPD)] are associated with an increase in the risk of requiring treatment for diabetes and of having to intensify therapy to include insulin," lead author Samy Suissa, PhD, from the Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital in Montreal, Quebec, Canada, and the Department of Epidemiology and Biostatistics and Department of Medicine, McGill University, said in a news release. "Therefore, patients instituting therapy with high doses of inhaled corticosteroids should be assessed for possible hyperglycemia and treatment with high doses of inhaled corticosteroids [should be] limited to situations where the benefit is clear."
The study authors note that although inhaled corticosteroids are recommended only for patients with the most severe COPD, current practice is that they are prescribed to more than 70% of all patients with COPD, including those with less severe disease. Because the prevalence of COPD and diabetes both increase with age, it is important to examine any possible interaction between inhaled corticosteroid use and worsened glycemic control.
Using the Quebec health insurance databases, the investigators identified a new-user cohort of patients treated from 1990 through 2005 for respiratory disease. Follow-up was through 2007, until diabetes onset, or until diabetes progression in the subcohort treated with oral hypoglycemics. To estimate the rate ratios of diabetes onset and progression associated with current use of inhaled corticosteroids, the investigators used a nested case-control analysis, with adjustment for age, sex, respiratory disease severity, and comorbid conditions.
Of 388,584 patients in the study cohort, 30,167 developed incident diabetes during 5.5 years of follow-up (incidence rate, 14.2/1000/year), and 2099 patients subsequently progressed from oral hypoglycemic therapy to insulin treatment (incidence rate, 19.8/1000/year).
Participants with current use of inhaled corticosteroids had a 34% increase in the rate of diabetes (rate ratio [RR], 1.34; 95% confidence interval [CI], 1.29 - 1.39) and in the rate of diabetes progression (RR, 1.34; 95% CI, 1.17 - 1.53).
The highest inhaled corticosteroid doses, equivalent to at least 1000 μg/day fluticasone, were associated with the greatest risk increases (RR for rate of diabetes, 1.64; 95% CI, 1.52 - 1.76; RR for diabetes progression, 1.54; 95% CI, 1.18 - 2.02).
Limitations of this study include possible residual confounding and the possible underestimation of incidence of diabetes.
"In patients with respiratory disease, inhaled corticosteroid use is associated with modest increases in the risks of diabetes onset and diabetes progression," the study authors write. "The risks are more pronounced at the higher doses currently prescribed in the treatment of [COPD]."
This research was supported by grants from the Canadian Institutes of Health Research, Boehringer-Ingelheim GmbH, and the Canadian Foundation for Innovation. Some of the study authors report various financial relationships with AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Pfizer, Merck Frosst Canada, Novartis, and/or Nycomed.
Am J Med. 2010;123:1001-1006. Abstract
Tuesday, December 14, 2010
Friday, December 10, 2010
Below is a paper showing scans causing disturbance in the blood brain barrier, linking bleeding/strokes to scan as well as causing damage to the endothelial cells.
Blood-Brain Barrier Disruption By Low-Frequency Ultrasound
Matthias Reinhard, MD; Andreas Hetzel, MD; Sebastian Krüger, MD; Stefan Kretzer, MD; Jochen Talazko, MD; Sargon Ziyeh, MD; Johannes Weber, MD Thomas Els, MD
From the Department of Neurology (M.R., A.H., S. Krüger, S. Kretzer, T.E.); the Department of Nuclear Medicine (J.T.); and the Department of Neuroradiology (S.Z., J.W.), University of Freiburg, Germany.
Correspondence to Andreas Hetzel, MD, Department of Neurology and Clinical Neurophysiology, University of Freiburg, Neurocenter, Breisacherstr. 64, D-79106 Freiburg, Germany. E-mail firstname.lastname@example.org
Background and Purpose— A recent study showed a dramatic increase in cerebral hemorrhage comprising atypical locations with low-frequency ultrasound–mediated recombinant tissue plasminogen activator–thrombolysis in humans. Here, we provide a possible explanation for this phenomenon by a side effect observed in a study using the similar ultrasound device.
Methods— The study was originally undertaken to investigate by transcranial Doppler sonography, positron emission tomography and perfusion MRI whether transcranial application of wide-field low-frequency ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral small vessel disease.
Results— Showing no clear positive effect on cerebral hemodynamics in 4 patients and on cerebral perfusion (positron emission tomography) in 2 patients, the study has been terminated early because of a remarkable side effect in the first patient (a 62 year-old man) undergoing perfusion-MRI: detection of frontoparietal extravasation of Gadolinium contrast agent (applied during MRI perfusion imaging preinsonation) on MRI immediately postinsonation.
Conclusions— Abnormal permeability of the human blood-brain barrier can be induced by wide-field low-frequency insonation. The observed excessive bleeding rate with low-frequency sonothrombolysis might thus be attributable to primary blood-brain barrier disruption by ultrasound.
Key Words: blood-brain barrier • hemodynamic phenomena • leukoaraiosis • side effect • ultrasound
Thursday, December 9, 2010
Mechanism of Grapefruit Juice Interactions
Basic Mechanism of Action
Drugs that interact with grapefruit and/or grapefruit juice (GJ) undergo cytochrome p450 oxidative metabolism in the intestinal wall or liver. GJ contains various furanocoumarins which have been demonstrated to affect the cytochrome p450(CYP) system (especially at isoenzyme CYP3A4) by binding to the isoenzyme as a substrate and impairing first-pass metabolism, by direct inactivation or inhibition of the enzyme (mechanism-based inhibitors). The net effect on the CYP enzymes from this inhibition seems to be a selective down-regulation of CYP3A4 in the small intestine.26 For certain drugs which are known to be CYP 3A4 metabolized, less drug is metabolized prior to absorption, and greater amounts of these drugs reach the systemic circulation, leading to higher blood levels, and potentially to increases in therapeutic and/or toxic effects.
Naringin is the main bioflavonoid in GJ. Naringin is not a potent CYP inhibitor, but is partially metabolized by enteral bacteria to naringenin, which is a potent inhibitor of p450 enzymes, and early research into GJ interactions proposed that naringin was the component of GJ responsible for the interactions,4-6 although it was thought possible that another unidentified component in grapefruit may also have been responsible, since giving naringin alone does not seem to cause the same degree of inhibition as GJ.4-5,21 Recent evidence clearly indicate that furanocoumarins, especially dihydroxybergamottin are the chemicals responsible for GJ interactions.
Researchers have isolated a group of compounds from GJ called furanocoumarins, which appear to be specific CYP3A4 inhibitors.27-29 A study on extracts of GJ interacting with rat and human p450 found that naringin accounted for only 10% of the inhibition of CYP activity seen with GJ.28 In vitro results show that a compound known as 6',7'-dihydroxybergamottin may be the chemical which accounts for the difference in effects on CYP3A substrates caused by GJ versus naringenin.27 A separate study with in vitro data determined that several compounds found in GJ inhibit CYP3A4 enzymes. Specifically, these were nootkanone (a sesquiterpene), and 4 derivatives of coumarin, geranyloxycoumarin, bergamottin, and 2 chemical with very long technical names, denoted as GF-I-1 and 4.29 Additional CYP3A inhibitory chemicals GF-I-5, GF-I-6 and bergapten have also been identified.132 The concentrations of nootkanone and bergamottin required to inhibit CYP3A4 enzymes however, was found to be higher than the naturally occurring concentrations found in GJ.
Results of confirmatory in vivo testing of CYP3A4 inhibition with externally administered GF-I-1, GF-I-4, GF-I-5 and GF-I-6 have not been published at present. It should also be noted that wide inter-individual variability in response to these interactions have been documented in studies.2,11
Start of New Article A recent study determined that the chemical moiety 5-geranyloxyfurocoumarine is essential for CYP3A4 inhibitory activity. This moiety is found in dihydroxybergamottin, as well as GF-I-1 and GF-I-4.127 A total of 6 furanocoumarin derivatives are suggested to be clinically active constituents of GJ.129
Commercial manufacturing of GJ is a multi-step process that includes washing of unpeeled fruit prior to squeezing whole fruits to juice. After squeezing, juice is heated for pasteurization, and volatile components may evaporate. Grapefruit oil, an important constituent of grapefruit peel, is sometimes added to the concentrate as a flavor enhancer.
A study found that epoxybergamottin, a furanocoumarin extracted from grapefruit peel is also an inhibitor of CYP 3A4. This compound has previously been found in only minor quantities in GJ, compared to 6'7'-dihydroxybergamottin. The authors note that it is possible that this compound could be distributed into the juice, during the commercial juice manufacturing process. Epoxybergamottin is not chemically stable in acidic medium, and may become hydrolyzed to 6'7'-dihydroxybergamottin.134
A study performed in cellular models indicates that GJ significantly activates p-glycoprotein mediated reduction in bioavailability, partially counteracting the CYP3A4 inhibitory effects of GJ.42 This experiment was performed in laboratory (CaCo-2) cell cultures, and was not a human trial. The results of this experiment were later found to be due to a laboratory artifact and were retracted132, though the retraction was not published by the original author. Subsequent results indicate that GJ likely acts as a weak p-glycoprotein inhibitor.
Start of New ArticleA recent study using GJ and digoxin shed further light on p-glycoprotein effects in humans. In a randomized crossover fashion, 12 healthy volunteers (7 male, 5 female) were given a single oral dose of digoxin 0.5 mg with either water or 250 mL of SSGJ 30 minutes prior to the dose, and 3.5, 7.5 and 11.5 hours after the dose. A two-week washout between study periods was employed.
Compared to the water group, mean peak blood concentrations (Cmax) rose 21%, time to peak level (Tmax) rose 8%, and total drug exposure at 48 hours (AUC48) rose 9%. None of these changes were statistically significant. AUC at 4 and 24 hours also rose 9% and this was considered statistically significant.
The authors consider GJ a weak inhibitor of P-glycoprotein, since studies with other known P-glycoprotein inhibitors show larger increases in digoxin AUC. They concluded that the study did not support the role of GJ as an important P-glycoprotein inhibitor, and that the modest increases in digoxin concentrations observed did not require any recommendations to alter digoxin dosing or titration when taken with GJ.114
Start of New ArticleIn a similar study, 7 healthy volunteers (4 male, 3 female) received a single oral dose of digoxin 1 mg with with either water or GJ in a randomized crossover design. A washout of two weeks between study periods was employed.
During the GJ phase, 240 mL of SSGJ was consumed 3 times daily for 5 days prior to digoxin administration, and 6 days after digoxin administration, in an attempt to maximize the effect on p-glycoprotein.
Compared to water, administration of digoxin with GJ showed peak blood levels (Cmax) decreased by a mean of 16%, total drug exposure (AUC) increased 3%, Time to peak concentration (Tmax) increased 25% and half-life was essentially unchanged (decreased by 3%). None of these changes were determined to be statistically significant, although significant interindividual variability was observed.
The authors concluded that when results are taken with the previous study, GJ ingestion does not have a significant effect on intestinal P-glycoprotein activity, and that P-glycoprotein inhibition does not play an important role in grapefruit interactions.115
Seville Orange Juice
Start of New ArticleA trial of administration of cyclosporine with GJ and Seville orange juice, both of which contain 6',7'-dihydroxybergamottin, was conducted recently. 7 healthy volunteers were given either water, single-strength GJ, or Seville orange juice 30 minutes prior to a 7.5 mg/kg dose of cyclosporine (Sandimmune® brand) in a randomized crossover design. The effect of Seville orange juice on CYP 3A4 concentrations in 2 individuals (via duodenal biopsy) and the effect of 6',7'-dighydroxybergamottin on p-glycoprotein activity in vitro were also assessed. The AUC for cyclosporine was increased 55% with GJ, whereas Seville orange juice did no significantly affect the AUC of cyclosporine. The two individuals who had duodenal biopsy showed clearly decreased enterocyte concentrations of CYP 3A4, suggesting that 6',7'-dihydroxybergamottin is not solely responsible for the increased cyclosporine levels when given with GJ. The in vitro studies confirmed that 6',7'-dihydroxybergamottin had no effect on p-glycoprotein.
So, if the two juices had similar concentrations of 6',7'-dihydroxybergamottin, why did cyclosporine blood levels increase with GJ, but not with Seville orange juice ? P-glycoprotein is known to play a significant role in cyclosporine availability, and based on this study, and in agreement with the study listed above, it is reasonable to conclude that GJ contains a compound or compounds that inhibit P-glycoprotein activity, which are not found in Seville oranges. Further studies are needed to identify inhibitors of p-glycoprotein in GJ and to evaluate the relative contribution of reduced p-glycoprotein and CYP 3A4 activity to the increased oral bioavailability of other drugs.51 Seville oranges may selectively "knock out" CYP 3A4 activity, while the inhibitor(s) of p-glycoprotein in GJ appear to be different from those compounds identified as inactivating CYP 3A4.132
Start of New ArticleEleven healthy volunteers (6 male, 5 female) received 30mg dextromethorphan daily for 5 days with either 200 mL single-strength GJ (study day 2), 200 mL seville orange juice (SOJ) (study day 4), or water (study day 1, 3, 5) in a linear, non-crossover fashion. Immediately, the non-crossover design raises a concern, since the effect of GJ on the enzymes is known to persist for 72 hours or more. A 3 -day washout was given after study day 2, and at least 7-days passed between study day 2 and 4. Blood levels were not collected in this study. Urine point assays, and 8-hour total urine concentrations were used to determine dextromethorphan availability in a complicated series of analyses, based partially on animal data, and some assumptions.
The fraction of the administered dose of dextromethorphan that escaped first pass metabolism were found to increase significantly and similarly when GJ or SOJ were taken with dextromethorphan on study days 2 and 4, although lack of an adequate washout period after GJ intake on day 2 was provided, the administration of SOJ with dextromethorphan produced an identical effect on the dextromethorphan pharmacokinetic profile as was observed with GJ. Two volunteers experienced drowsiness, but were found to be CYP 2D6 "poor metabolizers" (the alternate metabolic pathway for dextromethorphan and its metabolites). It also appears that both GJ and SOJ affected p-glycoprotein transport protein activity.94
Start of New ArticleTen healthy volunteers (5 male, 5 female) received a dose of felodipine 10mg with 240 mL of either fresh squeezed Seville orange juice, commercial orange juice, or grapefruit juice (diluted to contain the same total molar concentration of bergamottin and 6'7'-dihydroxybergamottin as the Seville orange juice). This study was conducted in randomized crossover design with at least a 7 day washout between study periods.
Seville orange juice increased felodipine AUC 76% and Cmax was increased 61%, compared to commercial orange juice (control). As expected, grapefruit juice increased felodipine AUC by 83% with Cmax increased 88%
An additional CYP 3A4 inhibitor, bergapten was found in seville orange juice, but not in grapefruit juice. Bergapten appears to have 1/3 the potency of 6'7'-dihydroxybergamottin when tested with midazolam in intestinal cell concentrations.132
Pomelo & Other Related Citrus Fruits
Start of New ArticleA case report exists of an interaction between tacrolimus and pomelo (also known as pummelo), a grapefruit-related citrus fruit. A patient taking tacrolimus post-renal transplant was stabilized on a tacrolimus dosage of 6 mg/day with tacrolimus blood levels stable in the therapeutic range of 8-10 ng/mL. A subsequent check of the tacrolimus level was increased at 25.2 ng/mL. The patient had no subjective symptoms. Upon further questioning, it was revealed that he had consumed approximately 100g of pomelo from his garden just prior to the tacrolimus on the day before blood sampling for tacrolimus level determination.117
Start of New ArticleFollow up testing by the above authors confirmed that some forms (1 of 3 tested) of pomelo juice extract were as potent inhibitors of CYP 3A4 as grapefruit juice extract in vitro. The pomelo extract had little effect on p-glycoprotein in a cellular model.124
Start of New ArticleIn 2004, Japanese researchers developed an enzyme-linked immunosorbent assay specific for coumarin derivatives that contain the geranyloxy- side chain, known to be the chemical moiety in grapefruit responsible for CYP3A4 inhibition. This allowed other fruits to be screened for containing 6'7'-dihydroxybergamottin.
Of 15 fruits screened, white grapefruit (control), red pummelo (pomelo), sweetie (oro blanco), melogold, banpeiyu pummelo, hassaku orange, sour (seville) orange, lime and natsudaidai showed significant immunoreactivity, indicating the presence of furanocoumarin derivatives. Navel orange, sweet orange and yuzu showed slight immunoreactivity, while iyokan orange, satsuma mandarin, ponkan mandarin and dekopon mandarin showed minimal immunoreactivity.
The researchers noted that besides the Rutaceae family (grapefruit-like) many plants of other families such as Umbelliferae, Leguminosae and Moraceae also contain furanocoumarin derivatives. Many plants of these families are used as common vegetables or traditional medicines, and it is possible that furanocoumarin derivatives contained in these plants could change the pharmacokinetics of certain drugs.129
Start of New ArticleIn a related study, Japanese researchers performed in vitro testing of local citrus fruits by incubating citrus fruit residue with human liver extract, midazolam, and measuring residual CYP 3A activity. Fruit juice residues prepared from banpeiyu pummelo, hassaku orange, takaoka-(suisho) buntan pummelo and kinkan (Tamatama) inhibited microsomal CYP 3A activity. Banpeiyu pummelo inhibition was strongest, though weaker than the white grapefruit control. No significant CYP 3A inhibition was noted with ama-natsu orange, dekopon mandarin, hyuga-natsu orange, unshu-mikan (satsuma mandarin) or navel orange. These findings are in agreement with the above study which looked at enzyme-linked immunoreactivity testing.130
Start of New Article In another related study by Japanese researchers, in vitro testing of tropical fruits was performed by incubating citrus fruit residue with human liver extract, midazolam, and measuring residual CYP 3A activity. Residues prepared from star fruit, pomegranate, and common papaw significantly inhibited CYP 3A activity. In all three cases, inhibition was stronger than the white grapefruit control. No significant inhibition was noted with valencia orange, mango, rambutan, kiwi fruit, dragon fruit or passion fruit.131
Time course of GJ-drug Interactions
Start of New ArticleA research group conducted a study with simvastatin to characterize the duration of the GJ induced CYP 3A4 inhibition. Ten healthy volunteers (9 male, 1 female) received simvastatin 40 mg with either water as a control, and either 0, 1, 3 or 7 days after drinking high-dose GJ (200 mL double-strength GJ) three times daily for 3 days in a non-randomized crossover fashion. As seen with the previous study, significant increases in simvastatin levels after GJ intake were observed on the day 0 study when compared with water. Simvastatin AUC was increased 1250%, with Cmax increased 1104%. Time to peak concentration (Tmax) was also prolonged from 2 hours to 4 hours (100% increase). This effect was significantly reduced if 24 hours elapsed between the last GJ intake and simvastatin dosing. At this time, simvastatin AUC was increased 105%, and Cmax was increased 136%. The authors noted that the effect of even high-dose GJ 24 hours after ingestion is only about 10% of that seen with concurrent GJ and simvastatin intake. AUC and Cmax of simvastatin when taken on day 3 and day 7 after last GJ intake were not significantly elevated compared to control, indicating that the interaction potential of even high amounts of GJ intake dissipates within 3-7 days after last GJ ingestion.
This is useful for characterizing the time course of GJ-drug interactions, and fits with prior expectations that the GJ effect can last up to 3 days after last GJ ingestion.90
Tuesday, November 30, 2010
By Jon Christian Ryter
June 19, 2010 NewsWithViews. com
http://www.newswith views.com/ Ryter/jon321.htm
PLoS Medicine a peer review journal for the Public Library of Science claimed in an article that the most respected medical journals have become much too dependent on revenue from the pharmaceutical industry from two sources. First, advertising revenue which, according to PLoS, is the least corrupting form of revenue since the pharmaceutical industry should have the right to reach their potential customers in the periodicals their customers-doctors- read. What is the bigger problem, and what corrupts the integrity of the advertising process in about 25 different medical journals according to PLoS in an article published by the Public Library of Science five years ago (but never read by the general public which does not generally subscribe to it) is the second source of "advertising" revenue. The PR firms hired by the pharmaceutical giants pay fees to the journals to print well-edited capsulated synopsis of the drug trials.
The PR firms know that when the drug trials are published in any medical journal, the drug and the test tacitly carry that journal's stamp of approval simply by appearing in it. According to PLoS, a favorable review in a periodical like the Journal of American Medicine and the British Medical Journal and Lancet which have global distribution is worth thousands of pages of advertising. The PR companies will sometimes pay upwards of a million dollars for reprints of the articles to send to drug distributors, pharmaceutical wholesalers and medical professionals. While the PR firms admit the recipients of the reprints seldom read them, what they rely on is the name of the prestigious journal printing the review of giving a new drug credibility in the marketplace it has not earned from evidence of their curative abilities. The more important the medical journal, the more credibility the drug receives in the eyes of the physicians who receive the reprints.
Many times the whole content of the written clinical tests are not all that favorable to the drug but that, of course, is not reflected in the capsulated, controlled synopsis that appears in the medical journals. In 1994, Dr. Paula Rochon, adjunct scientist for the Kunin-Lunefeld Applied Research Unit and several of her colleagues wrote a paper examining the impact of journals which were paid to publish controlled excerpts of clinical studies had on the medical community's acceptance of the drugs compared to actual medicinal value of the drugs examined. The study focused on one class of drugs only: nonsteroidal anti-inflammatory drugs designed to combat arthritis. They found 56 trials. Not one of the published reports on the clinical studies presented any facts that were detrimental to the drugs tested.
The group came back a decade later, in 2003, and did a follow-up study on the 56 trial drugs to see if the drugs were living up to their clinical claims. The article was published by Richard Smith, the CEO of UnitedHealth Europe. Smith was Editor-in-Chief of the British Medical Journal for 13 years and held that job when the aforementioned study on the new arthritis drug was done. In many cases the reality of the drugs did not match the printed rhetoric of the promises of the clinical study conducted a decade earlier.
The question raised by the Public Library of Science a decade later was: how do pharmaceutical companies get the results they want once the drug is approved and recommended by physicians to their clients. When we go to our HMO or PPO physicians and they prescribe medication, we assume-and have every right and expectation to assume-that the prescription our physician prescribes will relieve or cure whatever the prescription is taken for. According to Smith, the pharmaceutical companies and their PR firms get the results they want not by fudging the facts but by asking the right questions and providing the right answers. This comes from hiring the right PR top guns who know how to stay a step ahead of the peer review groups. They do this by isolating positive parts of the clinical studies and forcing the dialogue into those positive aspects while ignoring negative ones. Or they combine the results from different centers in multiple combinations to obfuscate negative results in some facet or facets of the clinical study.
These strategies, Smith noted, have been exposed in the cases of risperidone and odansetron. However, with the 56 clinical studies the PLoS were attempting to evaluate, there was an impossible amount of work to examine in order to ascertain how many of the trials were truly independent and not biased on behalf of the fees paid by the pharmaceutical company. Clearly, what the Big Pharma wants is their drugs approved and used, and the PR firms they hire are paid to get positive "reviews" from the medical journals and paid advertising and advertorial (paid editorial copy) in the form of capsulated clinical studies.
What it comes down to, if the world's most prestigious medical journals-which medical professionals read as the Bible of the industry-have sold their souls for money, it is no more factually believable than magazines like The Onion or Mad magazine, the satirical comic book most Americans of read as teenagers back in the 1950s and 1960s. Smith further noted that "...Journal editors are becoming increasingly aware of how they are being manipulated and are fighting back. But, I must confess it took me almost a quarter of a century editing for the BMJ to wake up to what was happening... [E]ditors ask for other related data [related to] the studies submitted to them...But editors do not know what other unpublished studies exist."
Editors generally do not know if they are doing an honest peer review on one product or on a gigantic clever marketing jigsaw. More than likely one or more editors have commented that the material they get, regardless if it's a precise document or a jigsaw puzzle will always be of high technical quality.
The question raised by Smith and investigators like Dr. Rochon is how do we prevent the most prestigious medical journals in the world from selling their editorial souls for money? How do we prevent them from becoming no more credible than Mad Magazine or The Onion? How do we prevent them from becoming an extension of the marketing arm of the pharmaceutical industry? Smith thinks the editors can demand the right to review the protocols, and insist that all trials be registered; and most of all, demand that all clinical studies are completely transparent.
That won't happen because the journal publishers and shareholders know those clinical studies are worth millions of dollars in revenue, and bring additional millions in print advertising dollars from the pharmaceutical industry to reward them for publishing the clinical studies. Meaning, of course, that the medical journals are not going to risk that revenue. So, if you're a doctor who generally reads the New England Journal of Medicine, the Annals of Internal Medicine, JAMA or BMJ or Lancet in England, Canada or Australia for the latest life saving drugs, you might as well read something that will give you a chuckle.
Mad magazine was my magazine of choice as a kid. Give it a try. You have to say one thing about Mad. If you're older than 8 or 10 years of age, you'll always know when Mad's story line is an out-and-out lie or is colouring the truth. According to Smith and the editors of several other medical journals, you can't tell that from clinical studies published in the medical journals until you read the histories of the drugs about a decade later. By then, for some, it's too late. I guess that's why class action lawsuits are still in vogue.
The whole structure of how research is conducted is shockingly flawed. A rebellion last year at Harvard University from medical students - against flawed theories heavily weighed on by Big Pharma. They wanted to study how to heal, not to maim!! A module at Kings College Medical School in London, teaching medical students how to interpret skewed statistical methodologies!!! That does not go far enough. Many of us, with a deep insight and mistrust of science, not only medical is pervasive.
Thanks to scientists such as Dr Ioannidis, making it possible for us, to understand and prevent further health disasters.
I came across this article (below) about a scientist, one of many, articulating succinctly what I found throughout my own hazy research on my quest for health.
My own observations is that most are ill because of medical interventions, and that, we have the an internal healing mechanism. The less it is interfered with, the more healing will take place. Tapping into the healing mechanism through means excluding medical intervention and prevention is of paramount importance. Its a personal choice. We are under constant assault from the time of conception. Parents who took vaccines and meds, environmental toxins, etc.. The mapping of the human genome proving to be a huge white elephant, and bla bla bla. My usual rant here.... ;D Anyhow, read this excellent article which mirrors my own and many of you there, thoughts on science, healing and so forth.
The article below encapsulates my own findings:
Lies, Damned Lies, and Medical Science
By David H. Freedman http://tinyurl.com/26olese
hat question has been central to Ioannidis’s career. He’s what’s known as a meta-researcher, and he’s become one of the world’s foremost experts on the credibility of medical research. He and his team have shown, again and again, and in many different ways, that much of what biomedical researchers conclude in published studies—conclusions that doctors keep in mind when they prescribe antibiotics or blood-pressure medication, or when they advise us to consume more fiber or less meat, or when they recommend surgery for heart disease or back pain—is misleading, exaggerated, and often flat-out wrong. He charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His work has been widely accepted by the medical community; it has been published in the field’s top journals, where it is heavily cited; and he is a big draw at conferences. Given this exposure, and the fact that his work broadly targets everyone else’s work in medicine, as well as everything that physicians do and all the health advice we get, Ioannidis may be one of the most influential scientists alive. Yet for all his influence, he worries that the field of medical research is so pervasively flawed, and so riddled with conflicts of interest, that it might be chronically resistant to change—or even to publicly admitting that there’s a problem.
In poring over medical journals, he was struck by how many findings of all types were refuted by later findings. Of course, medical-science “never minds” are hardly secret. And they sometimes make headlines, as when in recent years large studies or growing consensuses of researchers concluded that mammograms, colonoscopies, and PSA tests are far less useful cancer-detection tools than we had been told; or when widely prescribed antidepressants such as Prozac, Zoloft, and Paxil were revealed to be no more effective than a placebo for most cases of depression; or when we learned that staying out of the sun entirely can actually increase cancer risks; or when we were told that the advice to drink lots of water during intense exercise was potentially fatal; or when, last April, we were informed that taking fish oil, exercising, and doing puzzles doesn’t really help fend off Alzheimer’s disease, as long claimed. Peer-reviewed studies have come to opposite conclusions on whether using cell phones can cause brain cancer, whether sleeping more than eight hours a night is healthful or dangerous, whether taking aspirin every day is more likely to save your life or cut it short, and whether routine angioplasty works better than pills to unclog heart arteries.
But beyond the headlines, Ioannidis was shocked at the range and reach of the reversals he was seeing in everyday medical research. “Randomized controlled trials,” which compare how one group responds to a treatment against how an identical group fares without the treatment, had long been considered nearly unshakable evidence, but they, too, ended up being wrong some of the time. “I realized even our gold-standard research had a lot of problems,” he says. Baffled, he started looking for the specific ways in which studies were going wrong. And before long he discovered that the range of errors being committed was astonishing: from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals.
David Gorski, a surgeon and researcher at Detroit’s Barbara Ann Karmanos Cancer Institute, noted in his prominent medical blog that when he presented Ioannidis’s paper on highly cited research at a professional meeting, “not a single one of my surgical colleagues was the least bit surprised or disturbed by its findings.” Ioannidis offers a theory for the relatively calm reception. “I think that people didn’t feel I was only trying to provoke them, because I showed that it was a community problem, instead of pointing fingers at individual examples of bad research,” he says. In a sense, he gave scientists an opportunity to cluck about the wrongness without having to acknowledge that they themselves succumb to it—it was something everyone else did.
If a study somehow avoids every one of these problems and finds a real connection to long-term changes in health, you’re still not guaranteed to benefit, because studies report average results that typically represent a vast range of individual outcomes. Should you be among the lucky minority that stands to benefit, don’t expect a noticeable improvement in your health, because studies usually detect only modest effects that merely tend to whittle your chances of succumbing to a particular disease from small to somewhat smaller. “The odds that anything useful will survive from any of these studies are poor,” says Ioannidis—dismissing in a breath a good chunk of the research into which we sink about $100 billion a year in the United States alone.
And so it goes for all medical studies, he says. Indeed, nutritional studies aren’t the worst. Drug studies have the added corruptive force of financial conflict of interest. The exciting links between genes and various diseases and traits that are relentlessly hyped in the press for heralding miraculous around-the-corner treatments for everything from colon cancer to schizophrenia have in the past proved so vulnerable to error and distortion, Ioannidis has found, that in some cases you’d have done about as well by throwing darts at a chart of the genome. (These studies seem to have improved somewhat in recent years, but whether they will hold up or be useful in treatment are still open questions.) Vioxx, Zelnorm, and Baycol were among the widely prescribed drugs found to be safe and effective in large randomized controlled trials before the drugs were yanked from the market as unsafe or not so effective, or both.
“Often the claims made by studies are so extravagant that you can immediately cross them out without needing to know much about the specific problems with the studies,” Ioannidis says. But of course it’s that very extravagance of claim (one large randomized controlled trial even proved that secret prayer by unknown parties can save the lives of heart-surgery patients, while another proved that secret prayer can harm them) that helps gets these findings into journals and then into our treatments and lifestyles, especially when the claim builds on impressive-sounding evidence. “Even when the evidence shows that a particular research idea is wrong, if you have thousands of scientists who have invested their careers in it, they’ll continue to publish papers on it,” he says. “It’s like an epidemic, in the sense that they’re infected with these wrong ideas, and they’re spreading it to other researchers through journals.”
Though scientists and science journalists are constantly talking up the value of the peer-review process, researchers admit among themselves that biased, erroneous, and even blatantly fraudulent studies easily slip through it. Nature, the grande dame of science journals, stated in a 2006 editorial, “Scientists understand that peer review per se provides only a minimal assurance of quality, and that the public conception of peer review as a stamp of authentication is far from the truth.” What’s more, the peer-review process often pressures researchers to shy away from striking out in genuinely new directions, and instead to build on the findings of their colleagues (that is, their potential reviewers) in ways that only seem like breakthroughs—as with the exciting-sounding gene linkages (autism genes identified!) and nutritional findings (olive oil lowers blood pressure!) that are really just dubious and conflicting variations on a theme.
Most journal editors don’t even claim to protect against the problems that plague these studies. University and government research overseers rarely step in to directly enforce research quality, and when they do, the science community goes ballistic over the outside interference. The ultimate protection against research error and bias is supposed to come from the way scientists constantly retest each other’s results—except they don’t. Only the most prominent findings are likely to be put to the test, because there’s likely to be publication payoff in firming up the proof, or contradicting it.
..........That we’re not routinely made seriously ill by this shortfall, he argues, is due largely to the fact that most medical interventions and advice don’t address life-and-death situations, but rather aim to leave us marginally healthier or less unhealthy, so we usually neither gain nor risk all that much.
Read the whole article here: http://tinyurl.com/26olese
Thursday, November 25, 2010
Although it advises eating certain foods, such as broccoli for instance, many cannot eat most foods. Likewise, it advises taking oxidants, which risk turning pro-oxidants.
See article below:
This document was provided by
VOL. 5 No. 1
Once thought to be the seat of courage, love etc., the liver is central to our bodies’ endless process of removing unwanted chemicals. Leading British nutritionist and Director of the Society for the Promotion of Nutritional Therapy LINDA LAZARIDES takes a closer look.
One of our body’s most vital functions is to convert metabolic products and toxins into safe, soluble substances which can be eliminated via the urine or the gall bladder into the intestines. The liver plays an all-important role in this process – known as detoxification or biotransformation. Recent research has shown that many patients with chronic illnesses have a disordered liver biotransformation ability.
We simply don’t know all the diseases and health disorders which may be promoted by a toxic overload resulting from such dysfunction, but progress is beginning to be made in looking at specific detoxification pathways and relating underfunctioning of these to the development of disease.
A number of biochemical ‘pathways’ – sequences of chemical changes – are involved in liver biotransformation. These are normally grouped into oxidation, reduction or hydrolysis reactions (Phase I) and conjugation reactions (Phase II). Phase I reactions are catalysed by a group of liver enzymes scientifically known as cytochrome P450 oxidases (or P450 oxidases or cytochrome p450s). These enzymes introduce oxygen into the chemical structure of toxins or metabolites. Typically, by this process the toxins are converted into intermediate substances – alcohols and aldehydes – then into acids, which are water-soluble, and can be excreted via the urine.
Phase I detoxification
The intermediate substances created during Phase I detoxification, which include – far more so than the original toxins. Their harmful effects are primarily controlled by antioxidant nutrients/enzymes: a plentiful supply of these substances is essential. Apart from free radicals, intermediate metabolites include chloral hydrate (which is identical to the knock-out drug often known as a ‘Mickey Finn’), epoxides, and endogenous benzodiazepines – substances similar to Valium and other tranquillisers and sleeping pills. This makes it easier to understand how chronic fatigue, for instance, can develop when a toxic overload is present.
The more P450 enzymes are induced in the liver, the more of the toxic intermediates will be present in the body. P450 enzymes are induced by caffeine, alcohol, dioxin and other pollutants, exhaust fumes, high protein diets, oranges and tangerines, organophosphorus pesticides, paint fumes, steroid hormones, and a variety of drugs including paracetamol (acetaminophen), diazepam tranquillisers and sleeping pills, the contraceptive pill and cortisone.
Substances which can inhibit the action of P450 enzymes include carbon tetrachloride, carbon monoxide, barbiturates, quercetin and naringenin (found in grapefruit). The oxidation reaction can also be blocked by an excess of toxic chemicals, a lack of enzymes, lack of nutrients and/or loss of oxygen. Cant tolerate any of those either.
Such blocking results in a build-up of more toxic substances such as formaldehyde and other aldehydes in tissue. This can in turn lead to a spreading phenomenon, with increasing sensitivity to more chemicals such as ketones and alcohols, and eventually even to natural chemicals occurring in foods, pollen and mould. A build-up of aldehydes can in severe cases lead to tissue cross-linking, causing vasculitis with possible seizures and brain damage.
Although most aldehydes in the body are thought to occur as intermediate metabolites, external sources include exposure to formaldehyde gas (which is given off by new carpets, curtains and other furnishings) and breakdown products of ethylene glycol and methanol.
Two known sources of aldehydes are intestinal overgrowth with Candida albicans, as well as the peroxidation of polyunsaturated fats. The fatigue, foggy thinking and ‘brain fag’ linked with candidiasis may be due to an overloading of the detoxification system with aldehydes, which can even lead to a reverse reaction of aldehyde to alcohol. Extreme intolerance to alcohol consumption may occur in these individuals, as it does in those diagnosed with ME or chronic fatigue syndrome.
Cytochrome P450 and other oxidizing enzymes also oxidize amines such as phenylethylamine found in chocolate, tyramine found in cheese, and adrenaline, noradrenaline and dopamine. These are oxidized into aldehydes by the enzyme mitochondrial monoamine oxidase (MAO) – if this enzyme is blocked, for instance by MAO inhibitor drugs used to treat depression, tyramine, for instance, cannot be metabolized and hypertension can develop as a chemical sensitivity reaction.
Phase II detoxification (conjugation) There are five main conjugation categories, including acetylation, acylation (peptide conjugation with amino acids), sulphur conjugations, methylations and conju-gation with glucuronic acid. Some substances enter Phase II detoxification directly, others come via Phase I pathways.
Conjugation involves the combining of a metabolite or toxin with another substance which adds a hydrophilic (or water-reactive) molecule to it, converting lipophilic (or fat-reactive) substances to water-soluble forms for excretion and elimination. Individual xenobiotics and metabolites usually follow a specific path, so whereas caffeine is metabolized by P450 enzymes, aspirin-based medications are conjugated with glycine, and paracetamol with sulphate.
Acetylation requires pantothenic acid to function. It is the chief degradation pathway for compounds containing aromatic amines such as histamine, serotonin, PABA, P-amino salicylic acid, aniline and procaine amide. It is also a pathway for sulphur amides, aliphatic amines and complex hydrazines.
A proportion of the general population – perhaps up to 50 per cent – are slow acetylators. This rises to as high a level as 80 per cent among the chemically sensitive population. Their N-acetyltransferase activity is thought to be reduced, and this prolongs the action of drugs and other toxic chemicals, thus enhancing their toxicity.
Acylation uses acyl CO-A, with the amino acids glycine, glutamine and taurine. Conjugation of bile acids in the liver with glycine or taurine is essential for the efficient removal of these potentially toxic compounds. Disturbed acylation by pollutant overload decreases proper levels of bile in the gastrointestinal tract, resulting in poor assimilation of lipids and fat-soluble vitamins, and disturbed cholesterol metabolism.
Toluene, the most popular industrial organic solvent, is converted by the liver into benzoate, which like aspirin must then be detoxified by conjugation with the amino acid glycine (glycination): large doses of glycine and N-glycylglycine are used in treating aspirin overdose. Benzoate itself is present in many food substances and is widely used as a food preservative.
Glycine is a commonly available amino acid, but the capacity to synthesize taurine may be limited by low activity of the enzyme cysteine-sulfinic acid decarboxylase. Damage can occur to this enzyme directly by pollutants, or by overload/over-use resulting in depletion.
Both taurine- and glycine-dependent reactions require an alkaline pH: 7.8 to 8.0. Environmental medicine specialists may alkalinize over-acidic patients by administering sodium and potassium bicarbonate in order to facilitate these reactions.
Glutathione conjugation, using the amino acid glutathione in its reduced form, is used for the transformation of xenobiotics such as aromatic disulphides, naphthalene, anthracene, phenanthacin compounds, aliphatic disulphides – and the regeneration of endogenous thiols from disulphides. There is a cycle of replenishment for glutathione, allowing it to be reformed after conversion to glutathione reductase. Heavy metals can inhibit this cycle, thus preventing replenishment.
Sulphur conjugation (sulphation)
Neurotransmitters, steroid hormones, certain drugs and many xenobiotic and phenolic compounds such as oestrone (one of the forms of oestrogen), aliphatic alcohols, aryl amines and alicyclic hydroxy-steroids employ sulphation as their primary route of detoxification. Steventon at Birmingham University (UK) has found that many sufferers from Parkinsonism, motor neurone disease and Alzheimer’s disease as well as environmental illness, tend to have a reduced ability to produce sulphate from the amino acid cysteine in their body, and instead accumulate cysteine.
Sulphate may be ingested from food, but is also produced by the action of the enzyme cysteine dioxygenase on cysteine. This process is known as sulphoxidation.
The body’s ability to conjugate toxins with sulphate is ‘rate limited’ by the amount of sulphate present; if there is inadequate sulphate, toxins and metabolites can accumulate, perhaps building up to levels which cause degeneration of nervous tissue after several decades.
Steventon’s findings are a matter for serious concern. How many individuals are given the opportunity to find out whether they are poor sulphoxidizers and to reduce their chances of developing the above mentioned diseases by improving their sulphoxidation ability?
According to environmental medicine specialist William Rae, the process most often disturbed in chemically sensitive people involves methylation reactions catalysed by S-adenosyl-L-methionine-dependent enzymes. Methionine is the chief methyl donor to detoxify amines, phenols, thiols, noradrenaline, adrenaline, dopamine, melatonin, L-dopa, histamine, serotonin, pyridine, sulphites and hypochlorites into compounds excreted through the lungs. Methionine is needed to detoxify the hypochlorite reaction.
The activity of the methyltransferase enzyme is dependent on magnesium, and, due to the frequency of magnesium deficiency, supplementation with this nutrient will often stabilize chemically sensitive patients.
Glucuronic acid is a metabolite of glucose. It can conjugate with chemical and bacterial toxins such as alcohols, phenols, enols, carboxylic acid, amines, hydroxyamines, carbamides, sulphonamides and thiols, as well as some normal metabolites in a process known as glucuronidation.
For most individuals glucuronidation is a supplementary detoxification pathway. It is a secondary, slower process than sulphation or glycination, but is important if those pathways are diminished or saturated. Obese people seem to have an enhanced capacity to detoxify molecules that can use the glucuronidation pathway. However, damage to the capacity for oxidative phosphorylation which takes place in the mitochondria, is likely to diminish the capacity for glucuronide conjugation.
If the liver’s detoxification pathways are excessively stimulated and overly utilized, they eventually become depleted or begin to respond poorly – being suppressed by toxic chemicals. Once breakdown of the main pathways occurs as a result of pollutant overload, toxins are shunted to lesser pathways, eventually overloading them, and disturbing orderly nutrient metabolism. Chemical sensitivity may then occur, followed by nutrient depletion and finally fixed-name disease. Depleted immunity is also a potential outcome of a toxic overload.
• Dr William Rae of the Environmental Health Centre in Dallas says that the most severely ill chemically sensitive patients not only have abnormally low antipollutant enzymes, in addition to toxic suppression and nutrient depletion, but in some instances antibodies are produced against cytochrome P450 and these may inhibit or decrease its effectiveness.
• Environmental medicine specialists have found that almost 35 per cent of chemically sensitive patients are deficient in intracellular sulphur. Not only can this hinder the detoxification of some sulphur-containing and other toxic chemicals, it can enhance the harmful effects of exposure to cyanide from foods such as cassava and almonds as well as from tobacco products. The hereditary disease known as Leber’s optic atrophy involves a defect in the ability to detoxify cyanide, and leads to sudden, permanent blindness on first exposure to cyanide in small amounts such as those ingested from smoking cigarettes.
• Many multimineral supplements in the UK omit iron and copper due to theories that individuals may already be overloaded with these nutrients. However if no overload is present, an unbalanced supplement may promote depletion of the minerals. The Environmental Health Centre in Dallas finds that intravenous infusions to replenish iron stores brings dramatic improvements for the chemically sensitive patient as part of their detoxification process. Copper is also found to help catalyse the cytochrome systems. (NB: self-supplementation with iron and copper should be cautious, to avoid iron and copper overload conditions).
• Although the liver is the primary site for oxidation of xenobiotics, the cytochrome P450 system is found in other tissues that are exposed to environmental compounds like the skin, lungs, gastrointestinal tract, kidneys, placenta, corpus luteum, lymphocytes, monocytes, pulmonary alveolar macrophages, adrenals, testes and brain, in both the mitochondria and in the nuclear membrane.
• Always rinse your washing-up carefully. Pollutants in the form of solvents and detergents can damage and penetrate cell membranes and damage the contents of the cell.
• Vitamin B3 has been shown to accelerate the clearance of aldehydes in some chemically sensitive patients.
• Molybdenum, although an essential element, competes with sulphate in its activation step to the important enzyme PAPS and can thus lower sulphate levels and impair sulphation ability. Environmental medicine experts warn that molybdenum supplementation may be contraindicated in individuals with poor sulphation ability.
• The substance naringenin, found in grapefruit, can significantly inhibit Phase I detoxification, as can grape-fruit itself. This may prove clinically useful in some situations where Phase I activity is too high, (as shown in liver function tests available from nutritional therapists).
• Persons who have been exposed to toxic chemicals, drugs and other xenobiotics, have increased requirements for some vitamins. Functional nutritional assays for vitamins B1, B2, B3, B6, B12 and folate, and serum levels of vitamins A, D, C and beta carotene were performed in a random sample of 333 environmentally-sensitive patients prior to treatment. 57.8% were found to be deficient in B6, 37.7% in vitamin D, 34.9% in B2, 32.2% in folate, 27.7% in vitamin C, 21.4% in niacin, 14.9% in B12, 5.6% in vitamin A and 4.6% in beta-carotene. (Ross GH et al: Evidence for vitamin deficiencies in environmentally-sensitive patients. Clinical Ecology 6(2):60-6, 1989.)
Adapted from the Nutritional Health Bibleby Linda Lazarides (Thorsons, £9.99). Published September 1997. Available from all good bookshops or by mail order from SPNT Books (see address below).
Foods to aid detoxification
Beetroot helps with liver drainage
Broccoli, cauliflower and other cruciferous vegetables these aid cytochrome P450 activity
Radish, watercress rich in sulphur.
Supplements to aid liver detoxification
B complex vitamins
Digestive enzymes may be necessary to ensure that protein is adequately digested and glycine is readily available
Essential fatty acids
N-acetyl cysteine (NAC)
Selenium, zinc, magnesium and manganese possibly iron and copper if used with caution
Taurine (a useful combination product is magnesium taurate)
Vitamins C and E and beta carotene.
Liver herbs to aid detoxification
(traditionally known as ‘blood cleansing’ herbs)
Dandelion root cholagogue (stimulates liver secretions and bile flow)
Globe artichoke leaf promotes regeneration of the liver and promotes blood flow in that organ
Silymarin according to recent research, this herbal extract stabilizes the membranes of liver cells, preventing the entry of virus toxins and other toxic compounds including drugs. Promotes regeneration of the liver.
Turmeric a cholagogue like dandelion, but may irritate the gastric mucosa. Its advantages are its cheapness and ability to be used in cookery.
These herbs are best combined with wild yam, which helps to prevent liver spasms caused by gall bladder stimulating herbs.
For help with a liver detoxification programme, it is best to consult a nutritional therapist, who can arrange for (non-invasive) tests to determine which pathways need boosting.
For a list of nutritional therapists and other natural medicine practitioners in your area, send £1 plus sae to: Society for the Promotion of Nutritional Therapy (SPNT), PO Box 47, Heathfield,
acetylation – combination with acetic acid
alveolar macrophages – rounded granular phagocyte cells in the alveoli of the lungs that ingest inhaled particulate matter
aldehydes – a class of organic compounds containing the atomic group C(Carbon)H(Hydrogen)O(Oxygen)
amines – organic compounds containing nitrogen
amino acids – the chief constituents of proteins; the “building blocks” of life
biochemical pathway – a series of chemical enzyme reactions, that converts one biological material into another
Candida albicans – a quite common fungus in humans, which when unchecked can cause illness
catalyse – speeding up of a chemical reaction by a substance which remains after the reaction
conjugation – the joining together of two compounds to form another
corpus luteum – a yellow glandular mass in the ovary
dioxins – a group of chemicals present as trace contaminants in herbicides
endogenous – arising from within the organism
epoxides – compounds containing one oxygen atom bound to two different carbon atoms
ethylene glycol – a solvent used as an antifreeze
gall bladder – the reservoir for bile, on the surface of the liver
hydrolysis – the splitting of a substance’s molecules by adding water (H 2 0): a hydrogen-oxygen molecule (HO-) being added to one fragment, and the hydrogen atom (H) to the other
hydrophilic – readily interacting with water
intracellular – within cells
ketones – a class of organic compounds containing the molecule C=O
lipids – fats and fat-like substances
lipophilic – readily reacting with fat
lymphocytes – an immune-system cell generated by lymph tissue
metabolic, -ism – all the processes which create and maintain, and use up, organised living matter
metabolites – any substance produced by metabolism
methanol – a solvent
methylation – the addition of a methyl, i.e. a molecule of C(Carbon) and three H(Hydrogen) atoms
mitochondria – small cell organelles, with their own nucleic acids, that through synthesis of adenosine triphosphate (ATP) produce most of the energy for cells
monocytes – cells formed in bone marrow that travel to tissues, e.g. lungs and liver, to develop into macrophages
oxidation – the removal of electrons from the atoms of a substance; often by combination with oxygen
pantothenic acid – a member of the vitamin B complex
peptide – a compound of more than two amino acids
peroxidation – a chemical reaction creating an oxide with more oxygen than any other
polyunsaturated – denoting a chemical compound, particularly a fatty acid, having two or more double or triple bonds in its hydro-carbon chain
reduction – the addition of electrons to the atoms of a substance; often by combination with hydrogen
thiol – the univalient – S(sulphur)H(hydrogen) group
vasculitis – inflammation of a (usually blood) vessel
xenobiotics – substances foreign to the body
List of some Fluoroquinolones Antibiotics
Generic & Brand Name of most common Fluoroquinolones
Brand Name: Trovan - Zithromax
Brand Name: Factive
Brand Name: Zagam
Brand Name: Vigamox
Brand Name: Vigamox
Brand Name: Cinobac
Brand Name: Penetrex
Brand Name: Tequin
Brand Name: Levaquin
Brand Name: Floxin
Brand Name: Synercid
Brand Name: Trovan - Zithromax
Brand Name: Zymar
Brand Name: Avelox
Brand Name: Floxin Otic Singles
Brand Name: Ciprodex
Brand Name: Raxar
Brand Name: Ocuflox
Brand Name: Quixin
Brand Name: Cipro
Brand Name: Proquin XR
Brand Name: Requip XL
Brand Name: Zanaflex
Brand Name: Noroxin
Brand Name: Maxaquin
Brand Name: Ciloxan Ophthalmic Solution
Brand Name: Cipro XR
Generic Name Norloaxin Brand Name: Noroxin
Generic Name Temafloxacin Brand name Omniflox