Sources: Toxic Chemical Exposure Infographic
Chaé Organics May 28, 2013
Toxic Chemical Exposure Infographic
Sources: Toxic Chemical Exposure Infographic
Toxic Chemical Exposure Infographic
Sources: Toxic Chemical Exposure Infographic
Chaé Organics May 28, 2013
Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs
Prenatal exposure to Diethylstilboestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions.
Apple’s new iOS 8 Health app feature is an aggregator for HealthKit compatible apps in iOS 8. This may work great with “iWatch”
Apple’s new iOS 8 Health and Fitness app feature is an aggregator for HealthKit compatible apps in iOS 8. This may work great with “iWatch”.
DRUG JUSTICE – PHARMACEUTICAL COMPANIES SHOULD PAY FOR THEIR MISTAKES
” We are campaigning to have Grunenthal and Sanofi face their obligations and to stop hiding behind the protection of European legislation, face their responsibility and their guilt, and pay adequate compensation to the thousands of victims affected by their drugs.
The drug thalidomide – marketed for pregnant women suffering with morning sickness – was invented and sold by a German pharmaceutical company called Grunenthal between 1957 and 1961. Thalidomide killed most babies in the womb and those who survived are severely injured and disabled. The drug Epilim (Sodium Valproate) was marketed in 1973 as a drug for Epilepsy and to date has affected approx. 20,000 babies in a similar disastrous way.
Grunenthal has never compensated any British thalidomider. We ask that Grunenthal face their responsibility and give financial compensation to thalidomide damaged people in the UK. Grunenthal’s CEO must sit down with the thalidomide representatives and discuss financial compensation not just for the suffering and pain of living with thalidomide but also for the ongoing extra costs of living with the pain caused by thalidomide ”
The connection between Autism and Epilepsy
Little is known about the long-term outcome of epilepsy in autism and the epilepsy characteristics of adults with autism. This prospective population-based study was conducted in an attempt to point out differences on a group basis between adults with autism with or without epilepsy, and to describe the occurrence, the seizure characteristics, and the outcome of epilepsy in autism.
One hundred eight of 120 individuals with autism diagnosed in childhood and followed up prospectively for a period of 13-22 years were reevaluated at ages 17-40 years. As adults, the majority had mental retardation and autistic disorder or autistic-like condition. Interviews were performed with the caretakers of 42 of 43 individuals with a history of epilepsy, and their medical records were reviewed.
Adults with autism and mental retardation constituted a severely disabled group. On a group basis, both the cognitive level and the adaptive behavior level were lower in the epilepsy group than in the nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures with or without secondarily generalized seizures were the dominating seizure type.
In a community sample of individuals with autism followed up from childhood through to adult age, one of three had epilepsy since childhood/adolescence. Severe mental retardation and autism are significantly associated with epilepsy, especially in female patients. Seizure frequency has a great impact on the individuals’ lives. Specialist medical care is needed in this severely communication-disabled population.
Epilepsy occurs frequently in individuals with autism spectrum disorders (ASD). However, the mechanisms responsible for increased seizure susceptibility in ASD are largely unknown. Clues to neural hyperexcitability in the autistic brain might be derived from disorders in which single gene mutations cause both epilepsy and an autistic phenotype, such as fragile X syndrome and tuberous sclerosis complex. This chapter summarizes current understanding of epilepsy in individuals with ASD and explores potential links between the genetic disruption of neural circuits and cellular signaling pathways that contribute to both epilepsy and ASD.
Take Two Tablets Daily in blind Faith…
Benefits: unknown, Side Effects: unknown
Seen as a medical miracle to help women with pregnancy issues and a dependable source of steady income for pharmaceutical companies, Diethylstilbestrol (DES) was given to millions of women around the world. It was meant to be a wonder drug for expecting moms but its devastating impacts are now hitting their daughters and sons, decades later. Diethylstilbestrol was considered safe and effective for both mothers and their developing babies until the Food and Drug Administration (FDA) advised physicians in 1971 to discontinue prescribing diethylstilboestrol in pregnant women because of its link to a rare vaginal cancer.
Some professional groups and medical institutions are stressing the importance of counseling patients about both the potential risks and benefits of morcellation of a fibroid or uterus
Gynecologic surgeons, like many other surgical specialists, have embraced laparoscopic surgical techniques because they offer quicker recovery, less postoperative pain, and fewer wound complications than open procedures. The removal of large pieces of tissue through the small incisions of laparoscopy is difficult. However, this problem can be overcome by tissue morcellation, a technique of fragmenting tissue into smaller pieces that often prevents the need to enlarge established incisions. Surgeons have long used manual morcellation with a scalpel or scissors to remove masses abdominally and vaginally, but use of the technique has increased with wide adoption of laparoscopic approaches and with the introduction of laparoscopic electric morcellators in 1993.
Use of a surgical technique that involves cutting fibroid or uterine tissue into small pieces for extraction during minimally invasive surgery has come under scrutiny recently—scrutiny prompted by concerns that the process may disperse fragments of undetected malignant tumors throughout the abdominal cavity and upstage otherwise contained cancers.
Because it’s not possible to reliably detect the presence of uterine sarcomas before surgery, some experts say that use of the technique—known as intracorporeal uterine morcellation, which can be performed with an electric morcellator or by hand with a knife—may be too risky under any circumstance. Others say more research on risks associated with the procedure is needed before banning it outright. In the meantime, some professional groups and medical institutions are stressing the importance of counseling patients about both the potential risks and benefits of morcellation of a fibroid or uterus.
Images of the campaigners leading the fight to raise awareness of the Thaliomide scandal
2014 BBC documentary telling the little known story of a father’s battle for justice against one of the UK’s largest corporations.
Developmental exposure to BPA induces morphological, functional, and behavioral anomalies associated with reproduction
Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of in utero exposure to low, environmentally relevant doses of BPA on the development of female reproductive tissues in CD-1 mice. In previous publications, we have shown that this treatment alters the morphology of the mammary gland and affects estrous cyclicity. Here we report that in utero exposure to 25 and 250 ng BPA/ kg of body weight per day via osmotic pumps implanted into pregnant dams at Gestational Day 9 induces alterations in the genital tract of female offspring that are revealed during adulthood. They include decreased wet weight of the vagina, decreased volume of the endometrial lamina propria, increased incorporation of bromodeoxyuridine into the DNA of endometrial gland epithelial cells, and increased expression of estrogen receptor-alpha (ERalpha) and progesterone receptor in the luminal epithelium of the endometrium and subepithelial stroma. Because ERalpha is known to be expressed in these estrogen-target organs at the time of BPA exposure, it is plausible that BPA may directly affect the expression of ER-controlled genes involved in the morphogenesis of these organs. In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure.
” I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials. ”
There is a very informative and fascinating debate going on between Dr David Healy and Ben Goldacre regarding options, thoughts, strategies for better clinical trials access and transparency.
Dr. David Healy posted “fucked” here and I posted a summary here.
Dr Ben Goldacre responded here and here. I republished his reply here.
Dr. David Healy then clarified here – see below – I only added few related links (in the original text response) with the purpose to bring more clarity and/or references to the readers.
Again let me invite you to read “fucked” post 22 comments – about clinical trial data access and pharmaceutical industry transparency.
” The first point to make is this post isn’t about AllTrials.
AllTrials is a footnote.
It’s about the dismay that many felt at EMA backsliding. It’s about how it was obvious that something like this was on the cards. Against this background uncritical endorsement of industry looked like a bad idea. There was a desperate need to stay awake. It looks like too many of us have been asleep.
Ben offers an outline of the AllTrials strategy here. It’s helpful to have this.
His accusation that these posts misrepresent campaigns, smear people, shout abuse, and hector from the sidelines looks like a description of posts by others elsewhere. With very few exceptions any comments to the various posts on this blog that in any way fail to support Ben or AllTrials have been deleted.
The post repeated an alternate analysis – that the main thing industry wants to hide are adverse event data.
In a post 18 months ago I outlined how to achieve this industry would in public deploy the issue of patient confidentiality as a main justification for hiding data. In this it seems to me they have been assisted by Iain Chalmers editorial with Patrick Vaillance and now by Ben.
The historical evolution of the confidentiality issue is that the first informed consent forms said nothing about not showing your data to anyone else. Unnoticed industry have slipped in a “we will of course show your data to no-one clause”.
At the EMA conference on data access in November 2012, I made two points. The second was that industry would assert the notion of their privacy rights – which they have done. The other was that no one signs to have their data sequestered. Afterwards, Iain Chalmers congratulated me on the point – I thought we were on the same page.
Whether adverse event data is key or not, Peter Gotzsche through the European Ombudsman and Tom Jefferson and Peter Doshi through Tamiflu and RIAT seem to me to have done more in practical terms to move the issues forward than anyone else. It leaves me wondering why there is an endless call to celebrate Ben and not Peter or Tom.
Some of us have been working the GSK system and can see what the pitfalls are. Even if not redacted, this is a system that will make it close to impossible to analyse CSRs properly. But if it’s not proclaimed by AllTrials first it seems like such insights are unwelcome.
In several posts before the latest debacle I outlined how in my opinion there was a real chance that magnificent though he has been and clearly morally right, Peter Gotzsche’s efforts may do more harm than good. Even without taking GSK’s preposterous data access system into account, pushing for data adds to the undue premium being put on RCTs Twenty years ago the moral case for access was as strong and the risks consequent on failing were much less in that we were less hypnotized by RCTs than we are now.
Far from responding shrilly, Peter Gotzsche recognized the risk and we have been collaborating ever more closely since. The issues are so complex we might all be making mistakes – the only people unwilling to concede this seem to be AllTrials.
The push for data access remains morally compelling but there are other things that can be done that might be more effective.
As the BBC program a week ago on Thalidomide, and previous posts here, make clear, industry fear a boycott more than anything else. It is the only thing they have ever responded to.
At the moment the focus is on a bunch of bureaucrats in EMA, who aren’t there with a brief to protect us other than by regulating the wording of advertisements.
The focus should be on doctors who treat patients. We could refuse to use drugs where there is no access to the data. It shouldn’t even take courage to do this. In my opinion, this is the call that’s needed now rather than a call to support more of what AllTrials have been doing. But who will lead such a call?
Along with colleagues I put forward a softer version of a boycott – an AbbVie – which encouraged doctors and patients to use drugs but to report on the adverse events which would in fact make these chemicals better medicines. It would be difficult for government or anyone else to gainsay this win-win option in the way they might come out against the lose-lose of a boycott.
There is a conflict of interest here. RxISK.org has a stake in this idea. It was set up before AllTrials to move ideas like this forward. I suspect those of us working on RxISK in the evenings and at weekends have been putting far more hours into the effort than the AllTrials team have.
At the end of the day, I may well be wrong on this, but I personally think AllTrials have been naïve. I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials.
Recent decades have seen industry put Litigation Support Defences in place. As outlined a decade ago in Let Them Eat Prozac, putting a premium on clinical trials has been a key element in their litigation support strategy. Seen from this vantage point AllTrials offers Pharma a lot – all without the effort of having to conspire or fund a conspiracy.
Playing straight into industry’s hands is a hazard for all of us. Good intentions aren’t enough to save us. I’d rest more comfortably if the key players in AllTrials had a track record in bringing adverse events to light or even a record of supporting those trying to do so – if they’d really antagonized industry good and proper. It’s not that partnership isn’t nice but perhaps after playing hard to get first. ”