Category Archives: NSAIDs

SPECIALIST FAMILY PRACTICE CONSULTATIONS IN CLAREMONT/ HARFIELD VILLAGE CAPE TOWN

Dr Neil D Burman MBChB(UCT) 1966, MRCP(UK 1974) Senior  Family General (all-ages) & Internist  practitioner in Claremont Cape Town,  has left Grove Bldg moved his rooms to
 13 Stafford St Harfield  Village, 50m down from Harfield station subway above corner of 1st Ave. .
Consultations  by appointment only 1600-1800, sometimes from 0900 weekdays and public holidays/weekends.   .  Holistic integrative chronic natural medicine practice (HRT, pain relief, infection eg HIV AIDS, TB, /cancer/obesity screening & prevention) .
(No emergencies or surgery- these must go to nearest polyclinic or hospital ER). .

or consultations by Telephone/email  where appropriate.

appts: ph Reception office hrs  021 6717797.   .
or
doctor personal email doctor@healthspanlife.com  or sms or whatsapp (or as last resort  try ph) 0836299160 all hrs 07.00 – 21.00. .   or    or fax 0865657215
Fellow of  Kronos Longevity Research Foundation Phoenix Arizona.

MEMBER OF  Royal Society SA; Kidney Association;Faculty of Consulting Physicians of South Africa; Kingsbury Hospital Forum;  and Local & International Societies for Study of: ; Menopause and Aging Males, Hypertension, Sexual Health, Vitamin D3-Autoimmune Disease  CGCoimbra network;  SASIM SA Society of Integrative Medicine; LDN Trust; .  Insurance, and Professional Driving Permit Assessments. mornings SASSA Disability Grant med officer Cape Town Clinics.  (formerly practicing/lecturer  in Port Elizabeth;  Hypertension, Renal & Transplant  med   GSH UCT, Leeds Hospital  England: Tygerberg Hospital Univ Stellenbosch; Libertas Hospital G/wood; and Univ W Cape.

Preferred Provider: Discovery Health & FedHealth

UPDATE: FOR MILDER PAIN, WHY USE NSAIDS (LET ALONE DICLOFENAC) OTHER THAN PARACETAMOL -ACETAMINOPHEN?

update

Aspirin,  paracetamol, other NSAIDs,  and codeine  in periodic conservative analgesic use have  not been reported to cause hypoglycemia eg a few gm a day solo or in combination  in well adults-  despite  deliberate overdose of these being  notorious for causing fatal bleeding or  liver failure with hypoglycemia, or respiratory failure.

But increasingly tramadol is incriminated in dangerous hypoglycemia: Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain Fournier, Suissa, eaJAMA Intern Med.December      Tramadol is an increasingly widely used  weak opioid analgesic , associated with adverse events of hypoglycemia.  Analysis  in United Kingdom Clinical Practice of treatnent with tramadol or codeine for noncancer pain between 1998 and 2012  included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol  associated with  increased risk of hospitalization for hypoglycemia  in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). Conclusions  tramadol (in contrst to codeine), TRIPLED risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

update 4 March 2013  BAN DICLOFENAC?  four years on, another call comes  for the virtual banning of diclofenac, from no less than the Canadian Medical Association Journal , based on a new metanalysis of NSAID risks by University  Toronto’s McGettigan and Henry .

As this column has long pointed out, diclofenac is apparently still the only NSAID that can kill suddenly without warning.  There are many far safer alternatives eg naproxen, ibrufen; and no compelling clinical evidence or reason to use it let alone cox2 inhibitors  except false beliefs and heavy marketing.

So as this columnist concluded in 2009,  it is blatant fraud, negligence and potential indefensible homicide  to continue recommending  let alone  using diclofenac simply for profiteering.

21June 2009 It is 4 months since this column last addressed nonsteroidal anti-inflammatory drugs NSAIDs.

A new study (from USA, UK and Canada – Ray 2009) of NSAIDs  claims that in those with ischemic heart disease, the popular NSAIDS -diclofenac, ibuprofen or rofecoxib(Vioxx) – increased serious heart disease/ death by about 50-67% compared to nonusers; whereas naproxen over some 111000 patient years of use gives no significant risk or benefit.

A new study from Denmark (Fosbol 2009) this year looked at a million healthy individuals with no hospital admissions or selected therapy. Compared to no NSAID use, ibruprofen and naproxen gave no added risk of death/ myocardial infarction; diclofenac gave 67% increased risks, and the two coxibs (rofecoxib Vioxx; celecoxib Celebrex)  increased risk 100%.

So we are led to believe that naproxen or ibuprofen is the NSAID  mild-to-moderate analgesic  of choice. Naturally the American Colleges and academia – who represent the Disease Industry, not patients- recommend yet other potentially toxic drugs- like  the magical proton pump inhibitors- to counteract the adverse NSAIDS..

But is this just a myopic view beloved of big pharma, to promote their snake oils.?

Another new study from Denmark (Gislason 2009) of 110 000 patients after admission for heart failure in the 12 years 1994-2005, showed that 57% died; 9000 (8%) were rehospitalized with acute heart attack  and 40 000 (38%) were rehospitalized with heart failure. Thus heart failure in a well-nourished population has a poor prognosis. In 36 000 who had used NSAIDs compared to non-users, risk of death was doubled on  diclofenac; increased~67% on  (rofe-or cele)coxibs; and was  significantly increased 22-31% by all other NSAIDs including naproxen and ibruprofen.

It is common cause after 20 years that injected diclofenac is the only NSAID that can unpredictably cause sudden death. So it’s administration risks culpable homicide when it is totally unwarranted. No cases of sudden death from any oral NSAID   including aspirin appear on Medline, apart perhaps from the risk of hyperacute asthma (Asamoto 1999).

But what of gastrointestinal bleeding  risks of NSAIDS? a 2007 study in Japan (Yajima) scoped all orthopaedic patients who took NSAIDs for more than 4 wks: oral diclofenac increased risk of erosive gastric lesions sixfold. A new review from Seattle (Schlansky 2009) refers to Helicobacter synergism in all NSAID use.

WHAT IS THE NEED FOR NSAIDS? The Wikipedia entry on NSAIDs  sums it up: it has almost four times as much text on the numerous  adverse effects of NSAIDs as on their uses- in fact the  article does not discuss the advantages of NSAIDS as analgesics; in fact it states plainly  that alone  just  “their gastrointestinal effects  are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States”.

All designer drugs are dangerous in overdose. Without overdose, paracetamol has no risk – and the Wikipedia entry thereon is balanced and highly favourable even for infants. We know well that paracetamol- a fatal liver toxin in overdose- should not be marketed without a built-in simple liver (and antineuritic) protective of  eg (carbo-or N-acetyl-)cysteine, alphalipoic acid and vitamin BCo.  But the Disease – Big Pharma Industry is not interested in prevention- Only Disease Pays. And Regulators, lobbyists and legislators  protect their source of work and income- the Drug Industry.

Fish oil (EPA+DHA) is probably  the most beneficial NSAID supplement we have (- perhaps ahead of other front-runners like vitamins C, D, magnesium and CoQ10-) halving all sudden deaths, and reducing by at least a third all major chronic degenerative diseases from CVD to diabetes, arthritis, learning, depression, behaviour disorders. Industry wont pay for head-on comparative trials. But the trial evidence suggests that fish oil and oral EDTA have better risk-benefit than aspirin and other antiplatelet agents, NSAIDs and warfarin.

We know that for moderate trauma and small – medium (even knee) joint pain/  contusions, self-massage with any natural NSAID like arnica or wintergreen is all that is needed, combined if necessary orally with up to 3 to 4gm paracetamol /day +- if needed a little codeine.   Prior 2002 found no significant difference in pain relief between paracetamol and naproxen in tension headache.

For more serious pain,  short of strong opioids, there is in fact no overall trial evidence that weak opioids or NSAIDs are better than eg hypnotherapy, or acupuncture,  or judicious paracetamol; to which latter if necessary a little codeine can be added as step-up analgesia. The latter  agents have none of the deadly risk of NSAIDs. Amadio 1984 showed that of Peripherally Acting Analgesics: ” paracetamol at up to 4 g per day compares favorably in analgesic potency to aspirin and other NSAIDs, and  should be considered the treatment of choice for mild-to-moderate pain”.  Skovlund 1991 showed no significant difference between naproxen and paracetamol in postpartum uterine spasms.

Six RCTs – five in mostly European peoples and one in Hong Kong- found paracetamol equal to diclofenac (Voltaren) – March 1994 in arthritis; Brevik 1999 and Kubitzek 2003 in dental surgery; Hoogewijs 2000 and Woo 2006 after trauma; and Munishankar 2008 after Caesarian section.  In a Cochrane analysis 2003, Towheed showed that in the one placebo-controlled RCT in osteoarthritis, paracetamol was clearly superior to placebo with a similar safety profile. And the general principle of therapy applies, that if required, combination of analgesics from different groups is better than single drug therapy. But given the many potentially fatal risks of the NSAIDs – compared to paracetamol, opioids and if indicated  aspirin –  there is no compelling reason to add NSAIDs  for pain.

We know that it is negligent to initially sentence people with  spontaneous mild-moderate head/neck/backache or tendonitis at the shoulder, elbow, knee etc to bedrest, NSAIDS, opioids or referral for xrays, scans or surgery. 95% will settle rapidly with reassurance, posture instruction and simple topicals and paracetamol analgesia. Otherwise most pain will disappear with firm reassurance with brief simple laying on of hands eg massage and traction with gentle rotational manipulation and instruction in auto-reinforcement –  pressure point eg earlobe pressure, or acupuncture, or hypnosis. And most of the remainder resolve quickly with  simple targeted injection with a little local anaesthetic plus depot steroid.

And we know that with judicious use, topical corticosteroid injection – never mind judicious brief systemic steroid (corticosteroid, calciferol, testosterone) has little or no risk and far greater target and multisystemic benefit than NSAIDs; and for chronic conditions, like fish oil at least address the underlying pathogenic mechanisms/causes- whereas NSAIDs and paracetamol ignore these.

Is drug-speeded resolution of inflammation essential and beneficial except for the drug vendor? A careful RCT by Bradley ea from Indiana University in 1992 observed that “joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee osteoarthritis”.

So why are synthetic  NSAIDs and especially the Coxibs  still used? Why do academics and Regulators still allow, promote  them for  routine use, other than to profit Big Pharma, and cause perhaps a quarter million deaths a year globally?

UPDATE: SOME REMARKABLE LIQUID HEALTH SUPPLEMENTS – NOT STATINS BUT SULFUR-DMSO, LUGOL’S IODINE, FISH OIL and COCONUT OIL.

update 6 May 2014  see new insights at    DMSO – The Persecuted Drug by Dr. Stanley Jacob 27 Feb 2011

update 3  November 2013   IODINE DOSE AND DOSING:     the traditional approach is that of eg the Linus Pauling Institute at Oregon State University   and Wikipedia advocating the recommended daily allowance of 150 mcg  0.15mg a day for adults;  and the safe upper limit at ten times that intake;  but quoting  up to eg 7mg  a day  for treating fibrocystic breast disease; but  a single dose of ~100mg KI for nuclear exposure..
             But comprehensive discussion on maximum  iodine dosing by the Weston Price Foundation (2009) quotes  to much research, eg by MDs Dr Guy Abraham,  David Brownstein,  Broda Barnes ea – using for therapy  of disease  6.25mg up to 50mg/day, but historically up to 10gm a day (if this wasnt confusing mg with gm!).
             Dr Sarah Myhill in Wales UK  and Joe Mercola in USA put widely differing opinions and evidence  in perspective in 2013.
             The maximum available pharmaceutical grade 15% Lugols iodine contains about 100mg/ml ie ~10mg a drop, ie  a drop a week orally provides ~1.4mg ie 1400mcg a day- 10times the maximum recommended maintenance daily allowance RDA, although that is conservatively what healthy Japanese are estimated to ingest  in their traditional natural diet ..
          So the conservative  practical approach is to use 2% (Lugol’s) iodine ie containing 20mg/ml or 2mg per drop, about 1.3mg iodine/drop. While allergy to natural  iodine has apparently never been  reported, the prudent  might start with a test dab on the skin for using it as a paint. For oral use,  a test dose orally might be eg a teaspoon (4ml containing about 25 mcg iodine) of a mixture of 1 drop 2% Lugol’s in a glass of  water.
          Abraham and Brownstein 2005 reported Evidence that the administration of Vitamin C improves a defective cellular transport mechanism for iodine. This affirms the principle that no essential micronutrient  should be taken in isolation but ideally as part of good natural diet (now hard to achieve on the now traditional fast food genetically modified urban mass diet)- or with a balanced multisupplement including more realistic vigorous doses of vitamins C and D, and magnesium, selenum, boron, etc ..

UPDATE 18 JUNE 2013  Ji Sayer reviews    Evidence-Based Medicinal Properties of Coconut Oil

16 March 2013  THE THREE  OILS  SYMPHONY –  FISH OIL, COCONUT OIL, DMSO,- and EXPOSURE OF THE DEADLY OMEGA6 HOAX OF THE 20TH CENTURY:

this  “Three  Oils Symphony ” lacks references on virgin coconut oil. A comprehensive on-line synthesis  referenced to 1995 is by Dr Ray Peat.

Wikipedia puts in perspective the up-to-date  100% safe and multibeneficial virgin ie unprocessed cold-pressed  coconut oil versus the risks of  hydrogenated coconut or palm oils let alone omega6 oils. .
Fot those who have concerns about the safety, toxicology  of DMSO, the detailed randomized controlled trial of 1967-8 is exhaustively reported by Dr Richard Brobyn , confirming no serious adverse effects topically or systemicaly up to 90 days.
THE DEADLY HOAX OF OMEGA6  SUPPLEMENTS AND THE CHOLESTEROL HYPOTHESIS: A NIH team in Bethesda has just published a remarkable review in BMJ of the  Sydney Heart Study 1966-1973  with a review of recovered data, confirming that substitution of omega6  linoleic acid as safflower oil and margarine in modern marketed staple diet  was a monumental deadly marketing hoax for the past 50 years, since it almost doubled deaths in those men studied  from age 30-59 years. Wikipedia notes this deadly delusion  that safflower (oleic/ linoleic) oil is health protective. The same applies to oleic acid– high in olives, many nuts eg sunflower oil,  and animal fats especially when cooked- as Wiki summarises, excess omega6 increases the risk of breast cancer, and by Stephen Cunnane’s hypothesis, aggravates inflammation eg arthritis, cardiovascular and malignant, by worsening marine omega3 deficiency. .  This may not apply to some exceptional groups- Reverse epidemiology –  but is supported by hard science as weighed up carefully by Chris Masterjohn and his thoughtful dissection of Dr Daniel Steinberg’s  The Cholesterol Wars 
      These studies highlight one of the biggest marketing  Deadly Drug Hoaxes of the 20th Century, that lowering LDL cholesterol with  cholesterol-busters- statins –  is  necessary and beneficial for most people, for primary prevention 0f cardiovascular disease with average 1st world  population “mild to moderate” hypercholesterolemia.  When these synthetics-  statins -produce numerous serious adverse effects.  This contrasts with the legion benefits and zero adverse drug effects when natural anti-disease (anti-oxidant/ antithrombotic,  insulin-sensitizing  nitric- oxide promoting)   supplements- coconut oil, fish oil, DMSO, metformin, CoQ10, arginine, carnitine,  minerals and vitamins etc  – are combined in appropriate titrated doses.  .
IS FISH OIL BETTER THAN COCONUT OIL? PROBABLY EQUALLY IMPORTANT:

COMPARATIVE BENEFITS OF FISH OIL AND COCONUT OIL

Can anyone  find any published research that supports Peskin and Rowen 2011 book condemning fish oil supplement.,     and Dr Rowen’s article on Why Fish Oil makes you age faster?

Perhaps our expert ornithologists and sea researchers can find good support for their argument in birds and marine life- why do warmwater fish have so little marine oil?

there is still zero support  against good fishoil supplement for cooler climate populations on literature search.

a 2012  Univ Virginia  analysis  concluded that “With the possible exceptions of Vitamin D and omega-3 fatty acids there is no data to support the widespread use of dietary supplements in Westernized populations; indeed, many of these supplements may be harmful.”

But see the exhaustive favourable fish oil evaluation up to Jan 2012 at the Linus Pauling Univ oregon website .

and  recent new  papers  promote fish oil supplement- but mostly for people in the colder northern hemisphere or airconditioned cities, offices, factories, homes. .

Just two recent 2007/2009 papers express some doubt about the potential risk of fish oil triggering atrial fibrillation. But I have had worsening familial atrial fib for 23 years , and a tsp a day of cod liver oil helps control it.

I cant find any reference supporting their  argument that  pure modest-dose  fish oil supplement- as all authorities recommend. – is dangerous except Peskin’ and Rowens’.

BUT their argument may be valid for people who live in warm climates. South African cities are certainly not warm for much of the year; and the more industrious work in airconditioning when it is warm. Their argument  against fish oil supplement might certainly be valid for those who live in the tropics  outside cities   ie latin America, North and Central Africa, the middle east, northern India-Pakistan, accross subtropical asia and the near-equatorial  pacific.islands., who thrive on coconuts.

Peskin’s theory that low-freezing point  fish oil is essential only for denizens of the cold  deep may well apply also to human and animal inhabitants of the semi-arctic/antarctic land masses or living at cool high altitude like Mexico city.

It rings a bell with the opposite: coconut oil (melting point 24-26C) being staple food and so heathgiving for those living in hot (coconut palm) climates –  it thins in  more than temperate climates (20 to 40C) , hence may have a different protective lubricant/rheological effect to the vital antifreeze benefit of fish oil in  human and animal/marine dwellers living at -20 to <20C.  .

Thus it seems rational that I, we  now balance my 1tsp codliver oil a day with 1 desertsp  coconut oil twice a day, and advise  accordingly – the best of both oils. . .

for seriously ill pts I recommend up to 2gm fish oil concentrate 2x/day, with up to 60gm coconut oil twice a day, if tolerated. .

Rowen and Peskin’s  published references (other than vegetarian tribes that eat virtually no seafood) for their  contrary  viewpoint are in their 2011 book,

Does their theory  apply to more affluent people who live and work mostly in controlled temperatures (the mid twenties)  in 1stworld countries?  ..

So if you live in a hot city with warmed houses and offices, combining the two oils makes sense for you too.      Arctic  and antarctic circle outdoor dwellers certainly need their marine oil.

while Rowen supports Peskin’s  antifishoil argument,  analysis may justify both oils depending on the climate the population lives in eg fish oil in the icy latitudes, coconut oil in the triopics- and both in balance in the temperate zones.

In fact the Peskin-Rowen theory supports our policy to recommend both fish oil and coconut oil combined:

go back to the Peskin-Rowen book – even just their joint summation at the end: They stress that those who eat no seafood  and live long are 5 tribes  of humans:      vegetarian  Adventists- SDAs – who destress, and walk/exercise a lot and  also do not smoke, altho they may live in all climates in USA- where presumably they are mostly caucasians ; but  SDAs have total racial/tribal diversity . The other longevity claims  in closed tribal communities are heavily doubted. More recent researchers have concluded that  the older people get, the more they tend to exaggerate, confabulate  their age because it brings them eg more attention- eg the tribes Rowen/Peskin list – the Hunzas of Pakistan, Okinawans of Japan, Vilcambans of Equador, Abhascans of the caucasus, not to mention our own oldest old whether in tribal villages or in our cities. . That would explain why they live at such diverse altitudes and latitudes. And isolated tribal people are mostly poor,  dont have mechanized transport, and have to work outdoors till they drop,; and as % of their communities, the young leave to find work or get massacred/ conscripted, kidnapped, banished/ sold  as slaves   in wars against invaders, so their aging seniors are all that are left in those areas.

Peskin/Rowen ignore that by proven Darwinian evolution,  land-ambulant mammals evolved : from micro-organisms to eg mammalian coelocanths only about 400 000 years ago, in deep ocean waters, and hence are very oily.        But mammalian evolution dates back about 160million yrs;   and our endothermy– ability to thermoregulate  arguably dates from the dinosaurs and thus birds  about 300million years ago.

Perhaps human endothermic adaptation evolved when the first homo sapiens evolved at the tips of Africa and migrated from Africa around the globe some 10 000 to 100 000 years ago ( ie before and after the last Ice Age that started 40 000yrs ago and ended about 20 000yrs ago);  thus spreading from temperate  sunny  climates to cold semi-arctic lands of Europe, Asia, Iceland, Greenland  and Canada, and extremely hot equatorial/desert regions.

Hence we adapted from obligatory hot climate survival at up to 50C – the coconut eaters- to icy conditions down to -40C – who survived on  antifreeze fish oils as a staple. Fish oils freeze apparently between  18C    and -50C (DHA

update: 4 Feb 2013          HALOGEN AND HEAVY METAL IMBALANCE:
As radiologist  Dr Jeff Dach stresses now, Drs Abrahams and Brownstein and many others  have repeatedly reported the overwhelming evidence that          Iodine Treats Breast Cancer.  Whether this is taken orally, topically or most rationally both ways- by mouth and by deep massage driven in by DMSO- is  a matter of conviction and zeal.
Conversely areas with chronic iodine defciency– like Africa – have a high rate of goitre,  hypothyroidism through to obesity, vascular disease, growth impairment and cretinism- mental slowness and retardation. And perhaps not incidentally also have much higher rates of  endemic infections, fibrocystic breast disease, hypertension,heart and kidney diseases,  and cancer.
But while iodine supplementation in salt was a good idea elsewhere, salt overload is a major contributor to hypertension in black Africans,  so iodized salt is not the answer; and the fast food cult with salting and biltong – dried fish and meat – and cheap local cigarette smoking and alcohol – has worsened the hypertension problem.
It is increasingly recognized that it is the chloride rather than the sodium in salt that is the culprit in salt-related hypertension.  So we have  overload of three prevalent toxic halogens aggravating iodine deficiency here-  chloride in diet and as chlorine;  bromine that has crazily replaced iodine in bread; and fluorine added to drinking water where it is  not already toxically overloaded in fluorosis areas.
So far from just for thyroid deficiency,  iodine – plus selenium plus magnesium plus sulfur-  replenishment has become crucial both as  major anabolics, to reverse deadly   iodine deficiency,  and as  displacer-chelator (along with the century-old Nobel-prize winning EDTA)  of   deadly bromine, fluorine , lead, mercury, cadmium, iron and aluminium overload   (Guy Abraham) – all common in criminally polluted South Africa  where industrial warfare has ravaged the subcontinent since the late 19th century. .
Who cares about selenium supplements and balance? It is harrowing to see a recent study from Univ Pretoria that “A total of 896 maize grain samples were obtained from all the maize silos throughout South Africa (231 silos) and analysed for selenium (Se) content.  Of the samples analysed, 94% contained below 50 μg selenium/kg DM and can thus be classified as deficient from an animal and human nutritional point of view. Maize grain in South Africa is therefore a poor source of Se for animals and humans.”  Yet absorbable selenium deficiency is a critical factor in the risk of AIDS, let alone cancers and other infections.  The  art of selenium balance is to use organic selenium supplement, but unlike iodine therapy with multimiligram doses,  ,  no more than  400mcg/day selenium  to avoid selenosis.
These respective  elemental  overloads and deficiencies are incalculably big  problems in the prevalence of cancer, thyroid, osteoporosis,  dental, liver,  heart-renal-stroke and mental disease in South Africa, from violence (mad as hatters- endemic intoxication by smoking, alcohol,  cannabis, mandrax, meth  etc) and immune deficiency (endemic AIDS, TB, hepatitis, herpes) to steadily falling  school  attendance and academic results.
This in turn is catastrophically  aggravating the worsening poverty, unemployability, malnutrition and thus grant dependency  of the masses, and the worsening crisis in  the shortage of qualified and competent  administrators, politicians, scientists, lecturers, nurses  etc..
DMSO, Lugol’s iodine and coconut oil thus join fish- codliver oil -all with melting points around our comfortable habitat  temperature –  as a group of vital cheap antioxidant especially brain micronutrients for South Africa. And it is brains, intellect that  we all need above all else from conception to grave.

UPDATE 2 Feb 2013.    Dr Cynthia Koelker MD is a modern family practitioner in Ohio who muses on DMSO as effective non-prescription pain relief.                            A recent NaturalNews.com review  notes “Miracle cure’ controversy and why people should use DMSO for cancer, inflammation and more;  There is evidence that DMSO can cause cancerous cells to become benign.          DMSO can pass through human skin like water and enter cells. It can also stop or slow the development of cancers, such as breast, skin, bladder, colon, and ovarian cancer. Some people use it for cancer prevention. DMSO is used to help patients in withdraw from conventional cancer treatment and is promoted as an immune system booster.
Cancer centers use DMSO to protect healthy cells from chemotherapy and to decrease side effects from the deadly drugs. The DMSO Potentiation Therapy uses DMSO to allow chemotherapy to target cancer cells. This allows doctors to use extremely small doses of chemo, which lowers profits for the drug companies. No doubt the use of DMSO with conventional treatment, or better yet with other natural cures, is blocked because of the effect on drug profits.

A California research group in 2010  noted that Intractable and untreatable pain from cancer remains a challenge,  major impact on patients’ quality of life and survival. A significant number of patients receiving analgesic therapy with opioids report persisting pain of a higher intensity than the pain in those who were not on this class of drugs. DMSO is a naturally derived, inexpensive, non-toxic solvent and pharmaceutical agent that has been demonstrated to have numerous health enhancing and therapeutic benefits. In the present article, we provide the scientific evidence and substantiate possible application of DMSO as a well-tolerated excitatory modulator in the management of cancer pain. 

A 2009  North Carolina University study by   Satia JA,  White E ea. of supplement users over 10 years ie 770000 patient years showed surprising benefits in    cancer reductions with use of MSM   as well as fish oil, melatonin, St Johns Wort (all against colon cancer);   and chondroglucosamine (lung  and colon cancer) .    But  Garlic use associated with 1/3 increase in colon cancer.
 
Hence it is apparent that DMSO-MSM  – like coconut oil- is a major natural healer and potentiates many drug treatments  including against cancer and pain; and thus it follows that far lower doses of other medications may be needed if DMSO is used.

UPDATE:  27 January 2013  Stefanie Seneff ea at MIT point  out that   perverse modern industry has subverted agriculture and nutrition in                                         1. creating sulfur deficiency in crops (and thus in humans) through oversupplementing phosphate  at the expense of sulfur;                                                 2. driving down optimal cholesterol levels (ie cholesterol sulfate) through combined  obsssive futile cholesterol restriction and cholesterol-busters eg statins;  and                                                                                                                                              3.  the overload of fructose in processed food.   So increasingly both fast -processed -food eaters and the poor are sulfur deficient since they dont eat much food sulfur  –“eggs, onions, garlic, and leafy dark green vegetables like kale and broccoli, Meats, nuts, and seafood; Methionine, an essential amino acid, that we are unable to synthesize, is found mainly in egg whites and fish. A diet high in grains like bread and cereal is likely to be deficient in sulfur. This deficiency is worsened by acid rain and soft water- and worsens the epidemic metabolic syndrome, diabetes , vascular disease, Alzheimers,  and cancer.”   She reviews why these diseases are much lower in those living in volcanic  mountainous areas  eg Iceland, South America where sulphur abounds in food, and  along with enough ascorbic acid (also seriously deficient in processed foods)  is the backbone of vital cholesterol sulfate and its daughter sterols  (vit D3 sulfate, the corticosteroid and  sex-  and heart – ouabain- hormones). 

She points out the crucial role of iron sulfate in energizing cell metabolism by insulin and glucose, depositing needed cholesterol in cell membanes and promoting myoglobin  and brain strength instead of adverse tissue, hemoglobin and especially brain glycation  AGES – advanced glycation endproducts.

Is it surprising that (not just the rare  patients with serious hypercholesterolemia eg familial, nephrotic, cirrhotic  who needs statins)  but the progressive   deliberate successful poisonng of  the entire UK-USA population  with  statins by Big Pharma aided by the FDA and most Govt Regulators,  to drive down healthy average cholesterol levels to hypocholesterolemia,  is  notorious for causing brain fog, depression, fatigue, dermatitis, muscle pain/dissolution (rhabdomyolysis)  and liver-kidney- heart  dysfunction , while doing nothing to combat  insulin resistance, obesity and diabetes?

When –  instead of statins and other designer drugs  – to combat wasting diseases like infections eg AIDS and TB, cancer, diabetes (muscle wasting as fat accumulates), osteoporosis, atheroma,  heart/liver/kidney  failure and  neuro/muscular disease eg neuropathy, stroke, Alzheimers and muscular dystrophy-  what the population  needs is especially detox of heavy metal and eg estrogenic plastic overload;  more vitamin B, C , D3, K,  coQ10, arginine, carnitine, zinc, chromium  and magnesium, melatonin and GABA,  marine omega3,  sulphur in diet or as methionine/cysteine/DMSO/ MSM/glutathione;  and for serious lipidemia and resistant obesity at any age, metformin -dimethyl guanidine.

It is speculative  as to when nutrigenomics – ie costly genetic testing – is going to prove widely useful in real live clinical practice to provide useful diet guidance for our common lifestyle and  aging diseases.

Already in 1995 Shen and Murphy at Wisconsin University showed that while amyloid proten fibril deposits are a neurotoxic  cornerstone of Alzheimers’ disease in mice and man,  pure DMSO  totally prevents the formation of  amyloid betasheets at least in testtubes.

In 1999 Cherry ea  in Australia and 2004  House ea in Staffordshire confirmed the adverse effects of  aluminium and ferric deposits in Alzheimers;  and the potential benefits of heavy metal chelators like EDTA with enough magnesium  and calcium..  .

and by 2009 Gupta ea  in India showed also on the workbench that garlic extract – ie sulfur- both prevents amyloid sheet fibrillation and dissolves it.

So there are different safe  nutritional ways of  slowing if not dissolving amyloid plaques as well as atheroma plaques  in Alzheimeirs with combinations of  minerals, vitamins and other antioxidants/  chelators including sulfur foods like  DMSO, MSM and garlic.

Pine Tree Source v Fossil Fuel Source of MSM and DMSO:  Mike Pritchard-Jones in 2008 detailed the great but  academic debate .

But already by 1957, MacDonald ea at UCLA affiirmed the primary role of calcium and sulfur  in bone healing after fracture in rats. Yet the first Pubmed entry on sulfur deficiency disease in human nutrition – from a casava diet- is from Nigeria in 1968. and the latest from India  in 2012 from their  staple cereal-legume diet

A 2012 study Julien ea from Quebec and Greece shows important benefit of DMSO  against excessive tau phosphoprotein deposits in Alzheimers Disease.

Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins.

Like GABA,   Melatonin is a prime ubiquitous brain hormone that  (like the sex steroids ) also  declines  from age 30years, that profoundly maintains memory by preventing both hyperphosphorylation of tau protein and amyloid beta protein, in melatonin doses reported from 3 to 9mg/night.. theories about its therapeutic role go back 25 years on Pubmed.. so melatonin is conveniently combined with the supplement GABA before bedtime, while GABA is the ideal daytime anxiolytic for these distressed patients.

23 January 2013

For some time many of us have been taking and recommending the multisystem benefits of evidence-based natural micronutrients  – fish oil, coconut oil, vitamins, minerals,  and biologicals like HRT and  metformin –dimethyl guandine HCl – all  natural  supplements.

Now we have added medicinal natural DMSO liquid, the universal miscible solvent, never mind its crystallized sister form DMSO2-MSM.

DMSO   gives early and permanent preventative  benefits without risks in many musculoskeletal, cardiac and  neurological conditions. It is the only remedy registered in USA for chronic interstitial cystitis, and solely for that rare condition.  But it  is reported major benefit against trauma, thermal and radiation burns and scars, all infections, sinusitis-otitis, goitre, and pain including headache, gingivitis, dry socket; infertility from tubal blockage; dermatitis; burns, asthma; arteritis, arthritis, lumpy mastitis, diabetic and viral (eg shingles and herpes simplex) and other neuritis, and ischemic/varicose and diabetic ulcers and swollen varicose legs.

DMSO thus understandably has good synergy with the similarly anti-inflammatory antioxidants like tumeric,  fish and coconut oils; and metformin which also like DMSO and MSM crosses membranes well including into the brain.

We are seeing good pain and swelling relief with massage with combined DMSO + coconut oil+ zinc + Lugol’s iodine 15% including on scars and painful/lumpy breasts, head, neck, back, abdomen, joints, sprains, skin (pre)cancer etc. As usual one has to beware of too hastily overdoing movement after effective pain relief.

Ongoing experience suggests that sore or lumpy breasts including new painful lumps months after excision and radiotherapy be massaged  daily orinitially twice daily:  first with coconut oil, then Lugol’s (15%) iodine, then medicinal grade(98%) DMSO to improve deep penetration of the iodine to promote healthy tissue regrowth from deep. It is encouraging how tender  lumps disappear within days , including on repeat breast mapping with mechanical tactile Sure Touch scanning.

Adverse effects: apart from possible smell and taste (which some of us don’t experience), pure DMSO may cause redness and burning, as may strong iodine; this is avoided either by diluting the DMSO in a bit of water; or better by applying coconut oil first, then the iodine then last the DMSO.

One must be careful starting  with DMSO. Extracted from woodpulp, it is volatile, warms on mixing with eg the oils, or undiluted on the tongue. But there is no evidence of toxicity apart from the smell – which my metabolism apparently does not produce even on a tsp of 99% medicinal DMSO twice a day.. Megadoses of up to a gram per kg have reportedly  been used in severe conditions. Fair-skinned people are more sensitive to it so doses should be lower, starting with massage of sore/superficial lesions and/or just ¼ tsp by mouth. Any taste of it is obviously easily masked by mixing it with the essential oils (fish oil, coconut oil) and supplement powders listed, and whatever else is desired eg yoghurt, fruit squash or just water.

There are promising studies on Pubmed between 1989 and 2011 of the benefits of DMSO in management of prostate problems in rats, and humans for transrectal procedures , and intravenously as cancer adjuvant palliation. DMSO-MSM is cheaply and safely available

CHEMISTRY and further references::

DMSO2  MSoM  METHYLSULPHONYLMETHANE  C2H6O2S or (CH3)2 SO2  dimethylsulfone crystals melt @ 109C and boils @ > 238C. its Molar mass is 94,.  Density 1.45

DMSO MSiM METHYLSULPHINYLMETHANE C2H6SO Dimethylsulfoxide Me2SO crystals melt @ 19C , and boils @  189C      Its Molar mass is  78.  Density. 1.1

So the two dimethylsulfa sisters cost the same and  have the same benefits against pain, chronic cystitis, arthritis, brain trauma, radiation and cancer http://www.dmso.org/ .   But only the melted ie liquid form at household temperature is the strong penetrating solvent. It’s not clear whether oral DMSO gives better blood levels than DMSO2 –MSM, since only the DMSO is melted at body temperature whereas DMSO2 is not..

The purist argument against DMSO/DMSO2 as sulphur supplement is that sulphur is not an essential element. But this is obviously  fallacious since our chief components are the elements CHOPNS carbon hydrogen oxygen phosphate nitrogen sulphur- we cannot survive without ingesting these. Only plants and microbes can apparently photosynthesize living tissue  from CHOPNS by breathing  air and absorbing water.

MSO2 ie MSM has also been shown in humans to readily   cross the blood-brain barrier. In the rat DMSO carries diazoxide into the ischemic brain to mitigate hypoperfusion, and protects the brain against scute traumatic brain injury

Comprehensive updated review of DMSO to January 2013 from the USA Natural Medicine Database supplied by the Drug Information Centre of Groote Schuur Hospital UCT   echoes Steinberg’s review (Albert Einstein Med Centre in Philadelphi)  aAnn N Y Acad Sci. 1967;141:532-50 The employment of dimethyl sulfoxide as an antiinflammatory agent and steroid-transporter in diversified clinical diseases. that 90% DMSO massage in some 500 cases, gave overall good outcome in 80% with no serious or sustained adverse effects reported.

In particular, no evidence can be found overall in the accessible literature supporting one old report that a DMSO product was withdrawn in Japan because of cataract concerns.. A 2011 review of transdermal joint DMSO use from Arizona University found no evidence of human eye toxicity in their series or in the reported literature.

Studies on DMSO have been ongoing at University Oregon for >45years:

Ann N Y Acad Sci. 1967;141:214-20.The effect of DMSO e on the induction of breast cancer in the rat.  Fletcher WS, Dennis DL at Univ Oregon showed that in the rat, breast cancer induced by nitrobenzene was progressively reduced by 18months by DMSO 50ppm (ie 0.5%) in their water from after and even better from before the cancer was provoked. In humans this equates roughly to taking 10gm DMSO in 2L fluid a day..

JC de la Torre  in  1975 wrote “DMSO  has been tested in various experimental injuries of the central nervous system CNS in relation to other therapies. It appears  a useful drug in acute extradural mass-forming lesions, middle cerebral artery occlusion, respiratory anoxia, and spinal cord injuries, in rhesus and squirrel monkeys, dogs, and rats. The data from these studies suggest that in the experimental models, DMSO is clearly superior to no treatment, and appears to be more generally effective than other comparable treatments. No satisfactory answer has yet been found to explain the beneficial effects of DMSO…..”

and 2009  JC de la Torre and  SW Jacobs  Oregon University , ea  described  Pharmacology of DMSO in cardiac and CNS damage: “The pharmacological effects of DMSO administration include some desirable properties that may be useful in the treatment of medical disorders resulting in tissue injury and compromised organ systems. These properties include the reported effects of DMSO on impaired blood flow, suppression of cytotoxicity from excess glutamate release that may result in lethal NMDA-AMPA activation, restriction of cytotoxic Na(+) and Ca(2+) entry into damaged cells, blocking tissue factor (TF) from contributing to thrombosis, reduction of intracranial pressure, tissue edema, and inflammatory reactions, and inhibition of vascular smooth muscle cell migration and proliferation that can lead to atherosclerosis of the coronary, peripheral, and cerebral circulation. Review of the basic and clinical literature on the biological actions of DMSO in cardiac and CNS damage or dysfunction indicates that this agent, alone or in combination with other synergistic molecules, has been reported to neutralize or attenuate pathological complications that harmed or can further harm these two organ systems. The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease. “

Rheology is obviously crucial for health. . The lower the melting point and the higher the viscosity the healthier. Coconut oil (melts at 24C) and DMSO(19C) a universal solvent miscible in both water and oil have similar melting point well below the temperature of the healthy human (+-37C), while fish oil http://www.high-fortune.com/En-index-SW04.asp. melts at similar temperature (20C, freezes at 10C.)  Since the brain is about 20% omega3 ie fish oil, it perhaps explains why both coconut oil and DMSO with similar melting point and rheology –good flow- to omega3 have such profound benefit crossing the bloodbrain barrier and fighting vascular and inflammatory degenerative disease eg Alzheimers, as well as against cancer, which while supported by vascular growth factor VGF depend on hypoxia and thus acidosis..

PLoS One. 2012;7:e33361. doi: 10.1371/journal.pone.0033361. .Methylsulfonylmethane suppresses breast cancer growth by down-regulating STAT3 and STAT5b pathways.Lim EJ, Hong DY, Yang YM. Ea Konkuk University, Seoul, South Korea. Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which MSM inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers.

Invest Radiol. 2008:43::298-305..Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature.Cyran CC, Brasch RC ea. University of California San Francisco:  To evaluate the potential of quantitative assays of vascular characteristics based on dynamic contrast-enhanced magnetic resonance imaging (MRI) using a macromolecular contrast medium (MMCM) to search for and measure effects of dimethyl sulfoxide (DMSO) on cancer vasculature. treated control (n = 8) and DMSO-treated (n = 7) human breast cancer xenografts (MDA-MB-435) in rats were imaged dynamically by MMCM-enhanced MRI before and after a 1-week, 3-dose treatment course. CONCLUSION: Reductions in cancer microvascular leakiness induced by a 7-day course of DMSO could be detected and measured by dynamic MMCM-enhanced MRI and were confirmed by microscopic measurements of the leaked macromolecular agents in the same cancers. Results support the robustness of an MMCM-enhanced MRI approach to the characterization of cancers and providing first evidence for an in vivo effect of DMSO on cancer blood vessels.

Neoplasma 2004;51:460-4.Acetaminophen (paracetamol) and DMSO modulate growth and gemcitabine cytotoxicity in FM3A breast cancer cells in vitro.Bilir A, Guneri AD, Altinoz MA. McGill University, Quebec, Canada. Addition of antioxidants to chemotherapy is an unresolved problem in oncology. It is still an issue of debate, whether antioxidants may reduce rough cellular toxicity and thereby the systemic side effects of the chemotherapy, without sacrificing the anti-tumor efficacy.  Tumor-sensitivity towards gemcitabine a  new anti-cancer agent can be increased with anti-inflammatory agents.  Acetaminophen  and DMSO are two unique anti-inflammatory and anti- oxidant agents with unrelated structures,  both able to block RR and COX, simultaneously. we monitored efficacy of acetaminophen and DMSO to modulate growth and gemcitabine sensitivity in breast tumor cells, Peculiarly, acetaminophen alone stimulated S-phase, which was not accompanied with enhanced plating, rather resulting in 40.3% growth inhibition at the 96 hour. DMSO alone significantly diminished both the plating and S-phase, which resulted in 71.7% growth inhibition at the 96 hour. Gemcitabine drastically reduced S-phase and plating until 72 hours, yet at 96 hours it lost its efficacy to suppress the S-phase with concomitant 2-fold rise in cell numbers in comparison to 72 hour time point. Both DMSO and acetaminophen brought S-phase to around zero percent in combination with gemcitabine until 48 hours, yet they both reduced early cytotoxicity of gemcitabine at the same time interval. However, at the 96 hour, they both strongly augmented gemcitabine efficacy to block S-phase and prevented the rise in plating.

Oncol Nurs Forum. 1991;18:683-5.Case report: topical DMSO for mitomycin-C-induced skin ulceration.Alberts DS, Dorr RT  Arizona Cancer Center. Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors’ experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice.

MODERN SYNTHETIC PALLIATIVES- ANTIDEPRESSANTS,ANTIPSYCHOTICS, ANALGESICS, STATINS AND ANTI-INFLAMMATORIES – ARE RISKY NON-CURATIVE ESTROGENIC /FERTILITY ie METABOLIC ENDOCRINE DISRUPTORS

Accompanying his 32year old partner (with like her mother  BRCA+ breast cancer ), a   young man this week complains sorrowfully  of total erectile failure within three  days every time he resumes fluoxetine for longstanding depression.

This may suit those patients who eschew sexuality, who knowingly choose chemical castration.. But the drug doesnt fix the causes of depression, merely palliates, often no better than a placebo, sometimes worse- compared to natural multibeneficial  antidepressant supplements.

We already long  live in a sea of estrogenic endocrine disruptors decimating many species including humans,  like pesticides and PCBs, as so aptly described by Deborah Cadbury and Prof Nils Skakkebaek in classic books  eg The Feminization of Nature and The Estrogen Effect.

The commonest prescription  drugs (synthetics- antidepressants; major psychotropes;  amoxicillin,   oxidants ( betablockers eg atenolol;  nonsteroidal anti-inflammatory NSAID (which block antidepressant effects –the Paul Greengard hypothesis 2011 Rocherfeller Inst NY);  statins (cholesterol -steroid and insulin disruptors), and patent synthetic sex hormones-  are  now routine if not mandatory prescription  worldwide due to ruthless relentless marketing pressure-  disease-mongering for profit-  even in children, and worse,  in patients with cancers. The  commonest cancers- breast, prostate, uterus-  are estrogen-driven.

Such environmentally and biologically hostile designer patent drugs-for-profit   are increasingly detectable in surface wastewater globally  from human excretion, and thus drinking  water supplies .

Endocrine disruption studies of antidepressants  (eg fluoxetine Prozacs, mianserin Lantanon (its commercial analogue successor is now Remeron), Bupropion Wellbutrin Zyban;  Venlafaxine Effexor  and desimipramine)  in surface water in Canada,  USA,  Mexico, Brazil and Belgium since 2006, and longer for antipsychotics, statins  and NSAIDS, show estrogenic  ie antiandrogenic risks  for eg gender development and thus for breast/prostate cancer,   for  virility and fertility..

Doctors  mostly blithely  ignore that reproductive young females  have by evolutionary reproductive  necessity  100fold  lower androgenic:estrogenic balance (eg 3:1) than men (eg 300:1), and are also far more prone  than males both to estrogenic contraception prescription harm, and  to common  major depression and autoimmune disease like rheumatod arthritis and lupus, and thus to  the double peril of mutiple estrogenic  prescription.

Recently common NSAIDs eg ibrufen, diclofenac  and mefanemic acid have been shown to be estrogenic in fish.

But such elective  prescription of ( endocrine disruption) cancer- and infertility- promotors (antidepressants, NSAIDS, hormone contraception and HRT etc) ,  is hardly desirable or ethical  at any age, especially when patients and their parents  are not informed of the grave risks of these drugs with no proven longterm benefits (except for contraception).

new reviews  gives more insight  from a plastic surgeon into prevention, including the harms of xray mammography.

and into the gross dangerous overprescription  of diabetogenic depressing  hepato-nephro-myotoxic  statins for all.

Popular painkillers eg opioids like oxycodin, fentanyl, tramadol on the other hand are similarly also  powerful longacting hypoandrogenism–inducing drugs   promoting estrogen dominance – which further complicates the misery and depression of those in chronic pain or depression,  including from  cancer, especially in women as well as men;  who thus  require monitoring of gonadal hormone levels and, if deficient, testosterone replacement. Aloisi ea Univ Siena 2012.

ndb

Reprod Toxicol. 2012:34:80-5. In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.Müller JC, Imazaki PH, Boareto AC, Lourenço EL, Golin M, Vechi MF, Lombardi NF, Minatovicz BC, Scippo ML, Martino-Andrade AJ, Dalsenter PR.  University of Paraná,  Brazil.     .Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer.    Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
Pharmacol Biochem Behav. 2013103: 659-65..Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Lemini C, Cruz-López B, Martínez-Mota L  Universidad Nacional Autónoma de México, Mexico.Estrogen therapy may produce antidepressant-like actions, but the side effects, such as thromboembolic events, may restrict its use among women. The 17β-aminoestrogens (AEs) [prolame [17β-(3-hidroxy-1-propylamino)-1,3,5(10)-estratrien-3-ol)], butolame [17β-(3-hidroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol)], and pentolame [17β-(5-hidroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol)] induce estrogenic and anticoagulant actions, effects that could prove advantageous in an estrogen therapy; however, their antidepressant-like effects have not been described. The objective of this study was to determine the effect of these 17β-AEs (prolame, butolame and pentolame) in the forced swimming test (FST), an animal model sensitive to antidepressant drugs, and to establish the role of estrogen receptors in such actions. Ovariectomized female rats treated with prolame (10-200 μg/rat) showed a reduction in immobility and an increase in active behaviors in the FST, while this effect was not produced by butolame and pentolame (10-200 μg/rat). The antidepressant-like effect of prolame was similar to that of 17β-estradiol (E2, 5-20 μg/rat), sharing with it a biphasic profile but at higher doses. Antidepressant-like actions of prolame and E2 were not associated with changes in locomotor activity. With respect to a control group tamoxifen (15 mg/kg) by itself produced no changes in all behavioral evaluations, but canceled the antidepressant-like effect of prolame and E2. It is concluded that estrogen receptors participate in antidepressant-like effect of both estrogens in the FST. Antidepressant-like activity of different AEs is discussed considering their differences in chemical structure and the schedule used. Our results show additional central actions of prolame besides its pro-sexual, anti-coagulant, estrogenic and anxiolytic activity.
Aquat Toxicol. 2011:104::38-47. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Schultz MM, Painter MM, Bartell SE, Logue A, Furlong ET, Werner SL, Schoenfuss HL  The College of Wooster, OH   USA   Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish–a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Aquat Toxicol. 2010 ;100:354-64    .Waterborne fluoxetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus.nMennigen JA, Lado WE, Zamora JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL  University of Ottawa, Ontario, Canada.    Fluoxetine (FLX) is a pharmaceutical acting as a selective serotonin reuptake inhibitor and is used to treat depression in humans. Fluoxetine and the major active metabolite norfluoxetine (NFLX) are released to aquatic systems via sewage-treatment effluents. They have been found to bioconcentrate in wild fish, raising concerns over potential endocrine disrupting effects. The objective of this study was to determine effects of waterborne FLX, including environmental concentrations, on the reproductive axis in sexually mature male goldfish. We initially cloned the goldfish serotonin transporter to investigate tissue and temporal expression of the serotonin transporter, the FLX target, in order to determine target tissues and sensitive exposure windows. Sexually mature male goldfish, which showed the highest levels of serotonin transporter expression in the neuroendocrine brain, were exposed to FLX at 0.54μg/L and 54μg/L in a 14-d exposure before receiving vehicle or sex pheromone stimulus consisting of either 4.3nM 17,20β-dihydroxy-4-pregnene-3-one (17,20P) or 3nM prostaglandin F₂(α) (PGF₂(α)). Reproductive endpoints assessed included gonadosomatic index, milt volume, and blood levels of the sex steroids testosterone and estradiol. Neuroendocrine function was investigated by measuring blood levels of luteinizing hormone, growth hormone, pituitary gene expression of luteinizing hormone, growth hormone and follicle-stimulating hormone and neuroendocrine brain expression of isotocin and vasotocin. To investigate changes at the gonadal level of the reproductive axis, testicular gene expression of the gonadotropin receptors, both the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were measured as well as expression of the growth hormone receptor. To investigate potential impacts on spermatogenesis, testicular gene expression of the spermatogenesis marker vasa was measured and histological samples of testis were analyzed qualitatively. Estrogen indices were measured by expression and activity analysis of gonadal aromatase, as well as liver expression analysis of the estrogenic marker, esr1. After 14d, basal milt volume significantly decreased at 54μg/L FLX while pheromone-stimulated milt volume decreased at 0.54μg/L and 54μg/L FLX. Fluoxetine (54μg/L) inhibited both basal and pheromone-stimulated testosterone levels. Significant concentration-dependent reductions in follicle-stimulating hormone and isotocin expression were observed with FLX in the 17,20P- and PGF₂(α)-stimulated groups, respectively. Estradiol levels and expression of esr1 concentration-dependently increased with FLX. This study demonstrates that FLX disrupts reproductive physiology of male fish at environmentally relevant concentrations, and potential mechanisms are discussed.

Pharmacol Biochem Behav. 2008 ;88:332-40.Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats.Martínez-Mota L, Cruz-Martínez JJ, Márquez-Baltazar S, Fernández-Guasti A  Instituto Nacional de Psiquiatría  Mexico City In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17beta-estradiol (E2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E2 (5, 10, 20 and 40 microg/rat) or the combination of E2 [at sub-threshold (5 microg/rat) and optimal (10 microg/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E2 at the supra-physiological doses of 10 and 20 microg/rat produced antidepressant-like effects. E2 at 5 microg/rat (that re-established the levels of this hormone to physiological levels) and at 10 microg/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST.

Chemosphere. 2006:;65:1836-45.. Effects of the antidepressant mianserin in zebrafish: molecular markers of endocrine disruption.van der Ven K, Keil D, Moens LN, Hummelen PV, van Remortel P, Maras M, De Coen W. University of Antwerp,  Belgium.    Due to their environmental occurrence and intrinsic biological activity, human pharmaceuticals have received increasing attention from environmental and health agencies. Of particular, ecotoxicological concern are drugs that affect nervous- and endocrine-systems. Zebrafish genome-wide oligo arrays are used to collect mechanistic information on mianserin-induced changes in gene expression in zebrafish. Gene expression analysis in brain and gonad tissue clearly demonstrated the estrogenic activity of mianserin and its potency to disrupt normal endocrine (estrogenic) signaling, based on induction of molecular biomarkers of estrogenicity (e.g., vitellogenin1 and zona pellucida proteins). The possible mechanism underlying this estrogenic activity of mianserin is disturbance of the Hypothalamo-Pituitary-Gonadal (HPG) axis by direct interference of mianserin with the serotonergic and adrenergic systems in the brain of zebrafish. Taking into account the importance of the HPG-axis, and considering the concept of ‘critical window of exposure’, our results reveal the importance for more elaborate testing of endocrine disruptive effects of aquatic antidepressants at different lifestages and during longer exposure periods (e.g., life cycle studies). Although there is a low concordance between the gene expression results in this study and previous cDNA microarray hybridizations, the global mechanistic expression patterns are similar in both platforms. This argues in favor of pathway-driven analysis of gene expression results compared to gene-per-gene analysis.

 

J Hazard Mater. 2013 Jun 15;254-255:242-51. .Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish.  Ji K, Liu X, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Seoul National University,  Korea.This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

University of Algarve, Portugal  .buprofen (IBU) is one of the most sold over-the-counter non-steroidal anti-inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels’ gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels’ reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short-term reactive oxygen species (ROS)-generator.

 

Aquat Toxicol. 2011 ;105:264-9..Non-steroidal anti-inflammatory drug (NSAID) ibuprofen distresses antioxidant defense system in mussel Mytilus galloprovincialis gills.Gonzalez-Rey M, Bebianno M   University of Algarve,  Portugal.Active pharmaceutical ingredients (APIs) are presently considered an emergent class of environmental contaminants. Ibuprofen (IBU) is one of the most applied non-steroidal anti-inflammatory drugs (NSAIDs) in the world. Several authors report the occurrence of IBU in influents and effluents of waste water treatment plants (WWTPs), surface, river and public tap water in numerous countries. However, very little is known about the risks and chronic effects of IBU exposure in non-target organisms. This approach undertakes the assessment of several oxidative stress biomarkers responses through the analysis of antioxidant enzymes activities (superoxide dismutase – SOD, catalase – CAT, glutathione S-transferase – GST, glutathione reductase – GR) and lipid peroxidation (LPO) levels in sentinel species mussel Mytilus galloprovincialis gills exposed for 2 weeks to an environmental realistic concentration of IBU. Results clearly show the significant induction and positive correlation between SOD activity and LPO in exposed gills, concomitant to an antioxidant defense depletion of CAT, GR and GST compared to controls. The integration of all biomarkers in mussels’ gills separates non- and exposed groups supporting the breakdown of the redox defense system and IBU’s pro-oxidant action. Further studies are needed to test possible endocrine disruption effects in mussels’ reproduction fitness as IBU is involved on prostaglandins biosynthesis inhibition.

BMC Med. 2013; 11:57..  The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. CUNY School of Public Health  York, .Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.   METHODS:A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using ‘(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)’ restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.RESULTS:Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).    CONCLUSIONS:  Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.

 

Chemosphere. 2009 ;77 :1285-91.Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in Canadian sewage and surface water samples.  Lee HB, Peart TE, Svoboda ML, Backus S. Aquatic Ecosystem Protection Research Branch, Environment Canada      Rosuvastatin (RST) and atorvastatin (ATO) are prescription drugs and members in the statin family used for the treatment of elevated cholesterol levels. A method using solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of ATO, RST and its metabolite rosuvastatin lactone (RSTL) in sewage and surface water samples has been developed. In the influent and effluent samples collected from 11 sewage treatment plants located in Ontario, Canada, ATO, RST, and RSTL were detected in all samples with median concentrations of 166 ng L(-1) (influent) and 77 ng L(-1) (effluent) for ATO, 448 ng L(-1) (influent) and 324 ng L(-1) (effluent) for RST, as well as 158 ng L(-1) (influent) and 41 ng L(-1) (effluent) for RSTL. Due to the inter-conversion between RST and RSTL, the total concentration of RST and RSTL in a sewage sample should be reported. The median removal rate by wastewater treatment was 66% for ATO and 22% for RST and RSTL combined. These statins were quite persistent in sewage. After a storage period of 21 and 62 days, there was only a slight decrease in ATO concentration and no change in the total RST concentrations. These three compounds were also detected in a number of surface water samples at low ng L(-1) concentrations. This is the first reported occurrence and fate of RST and RSTL in the Canadian aquatic environment.
Ecotoxicol Environ Saf. 2011;74:1216-25. Chronic exposure to diclofenac on two freshwater cladocerans and Japanese medaka.Lee J, Ji K, Lim Kho Y, Kim P, Choi  Seoul National University,  Korea.
Consequences of long-term exposure to diclofenac up to 3 months were evaluated using freshwater crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). Marked decrease of reproduction was observed at 25 mg/L for D. magna, and at 50 mg/L for M. macrocopa. Three-month exposure of fish to 0.001-10 mg/L of diclofenac resulted in significant decreasing trend in hatching success and delay in hatch. The hatching of the eggs produced from the fish exposed to 10 mg/L was completely interfered, while fertility of the parent generation was not affected. Gonadosomatic index (GSI) of female fish was also affected at 10 mg/L. Predicted no effect concentration of diclofenac was estimated at 0.1 mg/L, which is a few orders of magnitude greater than those observed in ambient water. Therefore direct impact of diclofenac exposure is not expected. However its bioaccumulation potential through food web should warrant further evaluation.\
J Toxicol Environ Health A. 2009;72(10):633-41. Life-cycle exposure of fathead minnows to a mixture of six common pharmaceuticals and triclosan.Parrott JL, Bennie DT Water Science and Technology Directorate, Environment Canada,Fathead minnows were exposed for a life cycle to environmentally relevant concentrations of a mixture of six common pharmaceuticals and one personal care product (nominal concentrations: 1,000, 300, 100, 30, or 10 ng/L). Mean measured concentrations of each chemical in the highest fish exposure aquaria were: naproxen 793 ng/L, gemfibrozil 662 ng/L, diclofenac 331 ng/L, ibuprophen 217 ng/L, triclosan 115 ng/L, salicylic acid 67 ng/L, and acetaminophen (chemical analysis inconclusive, nominal 1000 ng/L). Fish exposed for a life cycle even to the highest concentrations of the six pharmaceuticals and personal care product (PPCP) mixture showed no significant changes in growth and development compared to control. Length, weights, condition factors, liver weights, and gonad weights of PPCP-exposed fish were similar to water and solvent controls (0.000005% ethanol v/v). There were no marked effects of PPCP mixture exposure on external sex characteristics of the fish or on egg production. The only parameter that appeared to be affected was percent larval deformities in F1, which showed a significant increase in the 100- and 300-ng/L (nominal) PPCP mixture. Larvae from control fish had 4.7% (water controls) and 3.4% (solvent controls) deformities, compared to 9.3% in the 100-ng/L (nominal) PPCP mixture and 9.2% deformities in the 300-ng/L (nominal) PPCP mixture. Chronic exposure to environmentally relevant concentrations of seven PPCP most often detected in Canadian municipal wastewater effluents (MWWE) did not appear to affect fathead minnow survival, growth, or egg production, although it produced quantitative increases in deformities in the F1 generation.
Hum Reprod. 1993 Aug;8(8):1168-72.Autonomic nervous modulation and effects of a prostaglandin synthase inhibitor on human cervical secretion.Jonsson B, Hammarström  Karolinska Hospital, Stockholm, Sweden.Modulation of cervical secretion at ovulation time was studied in 10 women with regular menstruations. In an in-vivo model with repeated collection of mucus samples during three 90-min periods, the amounts of mucus in a control cycle and in three experimental cycles were compared. Drugs interacting with the autonomic nervous system and a prostaglandin synthase inhibitor were administered at time of ovulation. The cholinomimetic drug carbacholine significantly increased cervical secretion, while the anticholinergic drug butylscopolamine markedly inhibited this secretion. A long-lasting decrease in secretion was seen after administration of the prostaglandin synthase inhibitor diclofenac. Beside regulation of cervical secretion by the ovarian hormones, these results suggest an autonomic nervous modulation of cervical secretion, and in addition an impact on cervical by a prostaglandin synthase inhibitor. The effects on fertility regulation in the female are discussed.
Water Res. 2010 Jan;44(2):555-66.   Oxidative transformation of micropollutants during municipal wastewater treatment: comparison of kinetic aspects of selective (chlorine, chlorine dioxide, ferrate VI, and ozone) and non-selective oxidants (hydroxyl radical).Lee Y, von Gunten U. Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland.  Chemical oxidation processes have been widely applied to water treatment and may serve as a tool to minimize the release of micropollutants (e.g. pharmaceuticals and endocrine disruptors) from municipal wastewater effluents into the aquatic environment. The potential of several oxidants for the transformation of selected micropollutants such as atenolol, carbamazepine, 17 alpha-ethinylestradiol (EE2), ibuprofen, and sulfamethoxazole was assessed and compared. The oxidants include chlorine, chlorine dioxide, ferrate(VI), and ozone as selective oxidants versus hydroxyl radicals as non-selective oxidant. Second-order rate constants (k) for the reaction of each oxidant show that the selective oxidants react only with some electron-rich organic moieties (ERMs), such as phenols, anilines, olefins, and deprotonated-amines. In contrast, hydroxyl radicals show a nearly diffusion-controlled reactivity with almost all organic moieties (k>or=10(9)M(-1) s(-1)). Due to a competition for oxidants between a target micropollutant and wastewater matrix (i.e. effluent organic matter, EfOM), a higher reaction rate with a target micropollutant does not necessarily translate into more efficient transformation. For example, transformation efficiencies of EE2, a phenolic micropollutant, in a selected wastewater effluent at pH 8 varied only within a factor of 7 among the selective oxidants, even though the corresponding k for the reaction of each selective oxidant with EE2 varied over four orders of magnitude. In addition, for the selective oxidants, the competition disappears rapidly after the ERMs present in EfOM are consumed. In contrast, for hydroxyl radicals, the competition remains practically the same during the entire oxidation. Therefore, for a given oxidant dose, the selective oxidants were more efficient than hydroxyl radicals for transforming ERMs-containing micropollutants, while hydroxyl radicals are capable of transforming micropollutants even without ERMs. Besides EfOM, ammonia, nitrite, and bromide were found to affect the micropollutant transformation efficiency during chlorine or ozone treatment.
Toxicol Appl Pharmacol. 2007 Dec 1;225:142-53. .Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, Hecker M, Murphy MB, Yu RM, Lam PK, Wu RS, Giesy JP.Michigan State University,       The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11beta2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11beta2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The beta-agonist salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

CHRONIC ILLNESS- MANAGED ANTIAGING & GENERAL PRACTICE CLINIC SOUTH AFRICA

update 6 April 2015

In Claremont  Cape Town

A  Specialist Family Internist Clinic offers consultations by appointment especially for managing (and ideally preventing)  the major chronic degenerative diseases of aging  and  maintaining physical, mental (and why not sexual?) vigour to a ripe and healthy old age; as well as preventing and managing acute disease at all ages.

The clinic (a specialist physician and a nutritionalist)  offers all-system evaluation and if available, natural  (as well as essential prescription orthrodox) prevention/treatment including metabolic – weight-endocrine-diabetes; heart-lung -kidney; hypertension; neurological-pain; joint & muscle; abdominal, immune system ie infection, cancer and auto-immune  support;  genito-urinary, & sexual problems;

and appropriate screening – ECG, non-xray ( no-touch thermography- eg thermomammogram;   SureTouch tactile) mammograms, non-xray (ie  ultrasound) BMD ie  bone fracture risk measurement, body composition, and appropriate hormone profiling/replacement.

Phone during office hours for appointment: for Claremont office  ph 021-6717415  or 6831465 (or 083-6299160) – at Grove Medical Bldg 1st floor no 15 (opp ABSA Bank Parkade c/o Grove Ave Pearce Rd)  , or neil.burman@gmail.com ;  or consultation by telephone/Skype or email .

by appointment only:        OFFICE HOURSby appt: ph office:  9am-5pm weekdays, 9am-1pm Saturdays.  AFTER  HOURS up to 9pm any day generally at office: –  email doctor   neil.burman@gmail.com  or ph 6am to 9pm  0836299160. EMERGENCIES  cannot be dealt with- acute emergencies and trauma, bleeding cases  must go to any  Emergency Unit .

Billing according to means ie specialist professional rates:  eg as a preferred provider for Discovery Health-  consultation procedure  0190; for needy patients, what the medical scheme pays  Detailed medical report and advice protocol provided at R300. Even Hospital Plans have to pay for outpatient consultation for scores of PMBs ie Prescribed Medical benefit conditions like Menopause.

 Needy patients desiring brief consultation can be seen by arrangement at GP rate.    Bone density scan  (covered by some medical schemes)  procedure 3612..  Non-xray mammograms are not yet covered by medical schemes codes: R650 for SureTouch including clinical consultation, R800 for thermomammogram.

SIMPLE SAFE LOWCOST RISK MEASUREMENT AND CORRECTION: THE SOCIOECONOMIC IMPACT OF OSTEOPOROSIS

  neil.burman@gmail.com

Already just since April 2010, Pubmed (the on-line catalogue of peer-reviewed medical journal papers)  reveals four reviews – from USA, Mexico, Ireland and Cambridge UK-  on the huge socioeconomic impact of neglect  of long-available safe cheap measurement  and prevention of osteoporosis in aging populations. Especially that osteoporosis is underdiagnosed, and hence the need for improved use of diagnosis screening and preventatives.

And another study  from France reviews the deadly potential cutaneous (let alone gastrointestinal and other) risks of bisphosphonate and strontium drugs  prescribed for osteoporosis . Their  risk of serious adverse effects  may be <1:10 000 – but no study has ever been done comparing such $billion raincheck designer drugs with simple balanced lowcost safe combination of the score of natural supplements (some 7 vitamins, about 8 minerals and 5 human biologicals- costing as little as about US$10 a month) that are proven to prevent and heal osteoporosis let alone have major benefit on most major chronic diseases. .

The analogy is so simple- one does not treat :

anything but major pain with opioids or risky non-steroidal drugs  (or a sore throat with antibiotics) when simple safe modest-dose non-addictive analgesics and local therapy suffice; or

overweight,  or type 2 diabetes , or common mild to moderate hypercholesterolemia with any designer drug but metformin until control (with diet, lifestyle, supplements including metformin and appropriate other hormone adjustments)  is no longer good enough; or

 mild to moderate  hypertension requiring drug therapy with anything but perfectly safe lowdose reserpine plus lowdose amilozide – which suffice in almost 90% of mild to moderate cases- when more modern designer drugs (eg betablockers, angiotensin-converting – enzyme inhibitors and even the older methyldopa and calcium channel blockers) and newer drugs  both have infrequent but serious adverse effects, and are   less effective (they do not have the long duration and safety record of reserpine plus amilozide that makes it so effective even with erratic use) .

The socioeconomic model that measures the impact of a therapy only on one disease eg osteoporosis obviously also by intent supports the global profiteering and job-creation interests of Big Pharma and their well-rewarded allies – Government, Regulators, Universities, Research, Corporations and private practice. For these big-money industries, the use of a safe shotgun of unpatented and nonprescription supplements that more than halves the incidence, premature disability and mortality of both fractures AND all the common major aging degenerative diseases is anathema, since it reduces the Aging Diseases Industry from a $trillion goldmine in the aging who still vote, travel and earn, to a $billion expense when it matters far less- in the very old.

Hence Big Pharma is fighting a global war to abolish free choice of foodstuffs and supplements, conspire with governments to dictate what sources of foodstuffs must be eaten, and put all micronutrient supplement under doctors’ prescription! and above all else, suppress comparisons of designer prescription drugs with the gold standard old drugs and highly effective safe combinations of supplements.

This column has regularly published the growing irrefutable proof that high technology appliances and drugs are simply not needed to measure, prevent and treat common fragility fracture risk or any of the associated linked common chronic degenerative aging diseases.

And Guglielmi ea from Italian and Singapore Universities recently published another landmark review  confirming the voluminous evidence,  recent reviews from UK, that quantitative ultrasound QUS scan has replaced Dual Xray DXA bone mass density BMD  scan as the goldstandard fracture risk measurement test in common practice . Portable lowcost and therefore far more widely available QUS avoids the irradiation risk of costly centralized DXA, and the increasing overreading of bone density and hence risk score with aging due to accumulating calcification over the lower spine and hips.

It is of course intuitively and logically obvious that QUS devices that fix the target bone at a standardized site between the QUS heads as with eg the heelbone in eg the Norland CUBA footbox will eliminate most performer technique variation with a manually moved contact as in eg the Sunlight Beammed system.

Southampton University UK has also just published a study showing good correlation between peripheral QUS measurement and direct bone density measurement of excised fractured femoral heads from elderly hip replacement patients. .  .

And a Madrid team has just published a survey showing good correlation in children between 5 and 12 years between QUS measurements  and calcium-vitamin D intake.

CONCLUSION:  Safe and lowcost QUS can and thus should be used for bone risk measurement at all ages and locations – including schools and even the bedside;  in contrast to DXA which must not be used in those who are pregnant or not  at least post reproductive if not post-middle-aged.

Even in    the chronically frail or mentally dependent, periodic QUS screening is as crucial as eg bloodpressure screening since eg hypertensive , elderly, dementing or stroke patients share so many risk factors, and are thus are even more prone to osteoporosis- and incidental osteoporotic fracture easily converts the walking wounded  from needing supervised care to being totally wheelchair- or- bed- dependent.

BIG PHARMA-US GOVT CONSPIRACY FRAUD: THE NEVER-ENDING STORY OF DESIGNER SNAKEOILS- VIOXXES, FOSAMAXES, PSYCHOTROPES…

neil.burman@gmail.com  20100630

Pharma Fraud: the saga continues:

So Merck is also paying out $4,5billion to settle Vioxx damage cases…

  and now    Fri, Jun 25 2010  Jury orders Merck pay $8 million Fosamax damages 

 But as this column has described for almost 3 years  now, over 3000 cases of bisphosphonate osteonecrosis had already been  reported worldwide by 2006; the first case having been reported in about 1996.    

    And  leading university clinician Professor Dr  Scott Reuben gets a slap on the wrist 6 month jail sentence and > $300 000 fine for consistently faking drug  results ( Vioxx, Bextra, Effexor and even Lyrica ) for Merck and Pfizer- to bolster their multibillions sales. How much has he been paid / guaranteed to retire luxuriously remains untold.  

 So Meck now leads Pfizer ($3.4billion admitted  so far) in fines and damages penaties-  but both Pfizer    and Merck  still face untold billions in fines and damages in current ongoing litigation against them.  And worse to come- Merck and Bayer face massive damages claims over their contraceptives . This apart from the bakers’ dozen of shady practices listed against Bayer, of unquantified costs.    

  I recently saw my first associated case, a postmenopausal woman who had to have all her teeth removed and implants done after they came loose after a  few years on a bisphosphonate for osteoporosis prevention.  But perhaps my mother-in-law’s spontaneous cornflake collapse  of her lower femur in 1998 was my first case, someone had put her at about 70years  on bisphosphonate a few years before. She has never walked since, despite repeatedly failed  knee replacement. .

  There never has been the slightest  proven clinical justification for taking Vioxxes- Celebrex- Voltarens for pain, or bisphosphonates for osteoporosis/osteopenia, since there are safe  long-proven more effective natural painkillers, and safe supplements which restore normal bone without any risks, and (unlike bisphosphonates) with multisystem benefits that reduce all major common  degenerative diseases by 1/3 to 1/2 .   These modern synthetic designer drugs like bisphosphonates,   nonsteroidal anti-inflammatory “painkillers” ,  statins- cholesterolbusters, hypoglycemic drugs which actually promote obesity, neuro-drugs like  Neurontin, Lyrica, and Prozacs – Effexors, were and are  invented  to deceive patients into taking  lucrative $billion-dollar a year patent prescriptions  for widespread “prevention” and treatment, instead of the original natural supplements like eg herbs, biologicals, vitamins,and minerals which give relief and address the real causes with minimal risks and at low cost.        

 This  catastrophic fraud of Big Pharma- fostered by governments (for massive tax profits, job creation and ‘kickback’- God forbid that they are called bribes ) is  now exceeded in size only by the biggest Big Pharma scam ever,   last year’s  false swine flu pandemic scam  set up between the US government and Big Pharma, with multibillion dollar profits from unproven-value  mass testing,  vaccination and Tamiflu of unknown future disaster potential like thalidomide and stilbestrol proved to be.    (which in turn is exceeded perhaps by the biggest scam ever of modern times- the 2nd Iraqi war of GW Bush-Dick Cheney- Donald Rumsfeld- Halliburtons   that has now run most of this decade, the $Trillion War of Jo Stiglitz which will cost future generations of American and UK taxpayers infinitely more than that in compensation for injuries and deaths and debt; when there never were grounds – other than limitless oil to be pillaged- to invade Iraq any more than any of another dozen repressive dictatorship, when the obvious target against  Al Quaeda was always Afghanistan-Pakistan. )  

And the USA Govt and WHO (and hence most countries’ sheep -like regulators) actually changed the definition of a pandemic last year to perpetrate the trill$megabillion  swine flu  scam, and forswore proper randomized controlled clinical double-blind trials  to justify the vaccines and Tamiflu; and conveniently declared masses of old vaccine stores that were legally past their expiry date as recertified for use; and actually indemnified the vaccine manufacturers they chose against any future liability for failure of or complications from the vaccines.  

 Thus  the current USA government -with the backing of coerced allied governments  – invented the so far unproven if not risky swine flu vaccines, then handed the  recipes over to chosen manufacturers for free to produce and make $billions each within a year- with no liability –  at the incalculable expense of present and future taxpayers already reeling under the onslaught of USA-provoked overseas wars and  gigantic banking and oil cartel scams carefully orchestrated  by  deliberately failed  government   “regulation” which have caused the worst western global financial depression and environmental pollution  ever. .  

But these Big Pharma mafia  companies are bigger than the economies of many countries – apparently up to >8% of American gross domestic product- so they are protected by governments as too big to  jail or  close for fraud!   They couldnt care less about a few billion dollar fines  and damages for which they budgeted under cost of business- eg Bayer  last year paid $68billion for Wyeth the HRT  (Premarin- Provera) giant in North America…  

 As this column has previously reported,  the late greatest economist of modern times Ken Galbraith  would have said that  Big Pharma truly  rerpresents   the bared  backside  of western capitalist social democracy Naomi Klein’s  disaster capitalism (led by the modern pioneers of Human Rights for their own citizens if not their vassal dominions  – UK, Europe and USA)   – –  at its foulest .