Twenty years on, post severe ADRs....and alive.

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.
http://health-quest.proboards.com/ 

A new FB site to discuss Lariam, and other toxicites
from medications.  All toxicities from medications,
in particular, Lariam and Fluoroquinolones antibiotics,
will cause damage to endothelial cells, oxidization,
oxidative stress, inflammation = diseases/illnesses.

https://www.facebook.com/groups/lariamorg/

Join and discuss your symptoms, medications, and
other less toxic models leading to reversal of toxicities.

Health Quest Forum
http://health-quest.proboards.com/index.cgi 

FB:
http://www.facebook.com/find-friends/browser/?rpix=1#!/profile.php?id=100002311715945 

HealthQuest Options

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.

DLA cuts--House of Lords UK Residents:

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.

Thanks.
Beebs

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.

sign here
http://epetitions.direct.gov.uk/petitions/20968
is the link to the petition.

twitter at http://twitter.com/PatsPetition

See Pat's Petition on FaceBook
http://www.facebook.com/patsepetition

Pharmacopoly

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!!

Watch live streaming video from projectcamelotlive at livestream.com

Health Quest Forum

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).

http://health-quest.proboards.com/index.cgi

FB: http://www.facebook.com/home.php#!/profile.php?id=100002311715945

The forum is an attempt at bringing all under one banner.


http://health-quest.proboards.com/index.cgi

FB: http://www.facebook.com/home.php#!/profile.php?id=100002311715945

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.

Why is the UK Government consistently refusing to release information concerning ME/CFS? Information held by the UK Government will be not be made public until 2076....

See few articles below about drug metabolism
and mitochondria.

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

1.
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: richard.kim@lhsc.on.ca.

Abstract

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
Abstract

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
drug-metabolizing enzymes.

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

Hyaluronic Acid eye drops may help with joints pains. It was reported that some experienced relief from this.

The article mentions Hyaluronic Acid in cream form for joints pains.

http://www.pingueculae.com/index.php/eye-drops/134-hyaluronic-eye-drops-supplements

In addition, since there is accumulation of uric acid in joints causing pains, it might be worth trying a diet low in purines:

http://www.ehow.com/facts_5004026_what-foods-have-uric-acid.html

Those of who have active EBV, HHV-6 following your ADRs from antibiotics, see the article below. There is strong evidence that antibiotics can reactivate the mentioned infectious pathogens. Its likely it activates other infectious pathogens, since antibiotics are immune suppressants. It seems that antibiotics dysregulate the immune system. Many complained of lyme disease symptoms, subsequently found to carry active Borrellia Burg, which were previously dormant.

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. carlsoa@mail.amc.edu

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.

http://www.ncbi.nlm.nih.gov/pubmed/16456....Pubmed_RVDocSum

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 post floxing!!

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
Abstract

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).
Introduction

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.[45] 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.
http://www.medscape.com/viewarticle/418295

Read more: http://noquinolones.proboards.com/index.cgi?board=theories&action=display&thread=1813#ixzz1EWiceWCj

Please send your ADRs stories to Public Citizen. You can choose anonymity or give as much info as you want.



If you or someone close to you has been harmed because of a medical error, please share your story.
Go to www.citizen.org/medical-error-stories

Its no wonder that so many suffer ill health or ADRs from prescription drugs....

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

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.

Summary

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
n.
Protection against the harmful effects of radiation.


radi·o·pro·tec
..... Click the link for more information., Terminalia chebula Retz., Phyllanthus emblica Linn. or Emblica officinalis Gaertn. and Terminalia bellerica (Gaertn.) Roxb.

Cont/.. http://tinyurl.com/4fyyfee

Another wonder cancer drug bites the dust!! None of these have shown to be helpful.

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!

Sources:
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.

Happy Holidays to everyone, and wishing you all a healthier 2011.

Study identifies prescription drugs associated with cases of violence
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

Buzzword "anti-oxidants" for the recent few years is holding pace. Some studies have shown that taking antioxidants can turn pro oxidants. The biochemistry is complex and complicated and further studies are needed for evaluation. So far, free radicals theories remain unconvincing, some are purely hypothetical based on conjecture. Caloric Restriction research shows promise, although its difficult to evaluate, since, it involves measuring life span of primates (non humans).

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
Abstract (provisional)

Background

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.
Methods

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.
Results

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.
Conclusions

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.

Several studies show vitamin B1 warding off kidney failure in diabetic patients*
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.
Abstract

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.

Watch out for these drugs on the FDA monitoring list:

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