Re: Breast Implants part 3

[Guest guest]

Dede,

I didn't know that implants kill your NK cells in order to fight Cancer!!

What can we take to replenish this? Stuff like Selenium????

Thanks for the information....pictures were horrible and made

me tummy turn a little though.

Love

In a message dated 3/7/2008 7:08:33 A.M. Eastern Standard Time, DGRAHAMA@... writes:

necrosis from silicone rupture

another breast with necrosis from implants

Implants are porous, and fluids flow in and out of them, creating

toxic soup. This goes for saline as well as silicone ! How quickly one

becomes ill from them depends on how good their immune system

is handelling all the toxins. Many get very ill, and dont realize that

it is because the implants have compromised the immune system.

Implant chemicals kill your NK cells, the ones that fight cancer.

Many of us have had several bouts of cancer. I am one of them.

I have had cervical, and colon.

Saline has a shelf life of 2 years. The Saline implants have valves

where they fill them up. These valves can be faulty and can have

bi-directional flow problems where fluids flow freely in and out of them.

http://www.fda.gov/cdrh/ost/reports/fy98/IMMUNOTOX.HTM

If you will read on the FDA site, you will find, under immuno toxicology

the truth about how implants disrupt the endocrin system as well as other things. It is NOT anywhere near where breast implants are, I guess the FDA didnt want people to make the connection......they are protecting

large corporation, and NOT the people ! ! !

Below is parts of the FDA article:

Endocrine Disruption by Medical Device Materials

Key words: estrogen disruption, uterotrophic assay, heat shock proteins, bisphenol A

CDRH is concerned with the potential for certain medical device materials to mimic or interfere with endogenous hormone actions. Because the hormone estrogen is a potent molecule having profound effects at remarkably low doses, assays are needed to assess the potential for harm from materials that may induce unwanted effects due to interference with normal estrogen homeostasis. OST scientists are collaborating with researchers at the Department of Biology, Washington University, on projects focused on improving the use of a key biomarker of exposure to estrogenic compounds and determining the characteristics of the estrogenic activity of bisphenol A, a plasticizer found in some medical devices.

OST scientists are modifying and enhancing the traditional assay for estrogenic effects. The traditional assay utilizes the ability of estrogen to cause a hypertrophy of the uterus in ovariectomized or immature female mice. The purpose of these modifications is to provide mechanistic information that will reduce the number of uncertainties in assessing risk from exposure to estrogenic materials. OST scientists are developing an assay that promises to do just that: obtain mechanistic information while examining estrogenic responses in the whole animal. This is accomplished by a side-by-side comparison of the traditional uterotrophic assay and a specific cellular event, the induction of stress proteins, that occurs when estrogen or estrogen-mimicking materials bind to its specific cellular receptor.

Stress, or heat shock, proteins are synthesized rapidly by most cells in response to various chemical and physical stressors, especially heat. This response is thought to serve a cellular protective function. Other functions have been found, and heat shock proteins are called "chaperones" because they appear to associate with other proteins and hold them in proper conformations. This appears to be their function in relation to steroid hormone receptors: they appear to hold the receptor molecule in an open position, so that the receptor can bind to ligand easily. When the ligand binds, the heat shock protein dissociates; the receptor is free to assume a new shape, one that retains the bound ligand but which also enables the receptor to bind the correct sequence on the genomic DNA, called the hormone responsive element. Thus, OST has tried to identify changes in heat shock proteins as a marker of estrogen receptor binding in tissues from whole animals treated with estrogens.

OST scientists have shown that such changes can be detected in a number of heat shock proteins in the uterus in response to estrogen and that the response is specific to uterine and estrogenic compounds. The effect of exposure time on changes in heat shock proteins was assessed in ovariectomized mice treated with estradiol, the primary estrogen form in the body. Increased relative uterus weight increased linearly between the 4-hour , 8-hour, and 12-hour post-exposure time points, and remained for 1 and 2 days. The histopathology of the uterine lining showed a similar pattern. Changes in the pattern of heat shock protein expression were observed between 6 and 12 hours post-treatment. Thus all three endpoints examined appear at approximately the same time after treatment. This is consistent with the idea that the heat shock protein changes are related specifically to the estradiol effects.

Other steroid and steroid-like compounds were used in order to examine the specificity of the response. The compounds included an androgen, an androgen-receptor antagonist, a progestin, and a partial estrogen. These compounds induced changes in heat shock protein expression, but did not induce uterine swelling. This result demonstrates that the heat shock protein changes are not the result of the stresses to the cells caused by uterine swelling, and the heat shock response may be more sensitive than the uterine response. Compound ICI 182,780, a potent anti-estrogen, had no effect on uterine weights and did not induce changes in heat shock proteins. However, the highest dose of the ICI compound blocked the uterine and heat shock protein effects of co-administered estradiol. Thus heat shock protein induction: 1) is an estrogenic effect independent of uterine swelling; and 2) is a more sensitive indicator of estrogenic effect than is uterine swelling. The histological changes occur in parallel with the uterine swelling effects.

The three endpoints (uterine hypertrophy, histology, and stress protein expression, were used to examine the estrogenic response of the plasticizer bisphenol A. Bisphenol A was determined to be less estrogenic that estradiol (by more than 1000-fold), but caused similar effects. Histological changes in the uterine epithelia were observed at doses 40-fold lower than doses that caused uterine swelling. Although responses were variable, heat shock protein induction was also more sensitive than the uterotrophic response.

Immunological Responses to Silicone Breast Implants

Key words: autoantibodies, silicone breast implants, immunopathology

The breast implant experiments were accomplished in two parts: first to demonstrate immune responses to silicone gel implants in an animal model; and second, to apply the experimental protocols to samples from women with/without breast implants. The objective of these studies was to determine which autoimmune-like symptoms and other symptoms are associated with implanted materials.

OST has developed a rat model to study and understand immune responses to silicone gel and oil used in breast implants. This model included normal rats and a strain of autoimmune rats, that mimicked clinical conditions found in patients with silicone gel breast implants. Mixtures of silicone gel/oil were injected into the mammary area of female rats. Scientists then measured the levels of autoantibodies to collagen and to nuclear proteins developed over 2 years in response to these mixtures.

Results from the rat model indicate that specific autoantibodies may be induced by certain biomaterials. The immune system recognizes a biomaterial-connective tissue protein association as altered-self or as foreign. OST scientists have demonstrated that medical grade silicone oil can stimulate serum autoantibodies against collagen and against DNA when this oil is injected into mammary tissues of rats. Autoantibody production against connective tissue proteins is an immune response that is consistent with reports from women with silicone breast implants. The results also demonstrated pathological changes in animals that may result from the autoimmune response and that silicone gel can migrate to distant anatomical sites or localize at the implantation site. This work has been presented at The FDA Science Forum, The American Association of Immunology, and The American Association of Biochemistry and Molecular Biology.

The implication from these findings is that leaked oil from a breast implant via leaching or with rupture might provide stimulus for the production of autoantibodies in clinical patients. Therefore, OST scientists evaluated autoantibody levels (in blinded experiments) in serum samples from 150 patients representing four groups: women with silicone implants without connective tissue disease, women with silicone implants with connective tissue disease (CTD), women with connective disease but no implants, and healthy women volunteers. Results from these experiments show in a statistically significant manner that elevated autoantibodies to collagen type I, collagen type II and anti-DNA were detected in serum of patients with CTD, CTD + silicone implants, and silicone implants without CTD.

Using two different assays, autoantibodies to connective tissue proteins (e.g., collagen) and to DNA and intranuclear proteins have been detected in women with silicone breast implants. Historically, there is a strong correlation between anti-nuclear antibodies and clinical symptoms of some autoimmune diseases. OST has documented serum immune responses in these patients with the goal of enhancing the ability to predict the likelihood of immunotoxic symptoms occurring in the presence of implants, including breast prostheses. This work has been presented to the Institute of Medicine.

OST scientists are continuing to investigate these results by correlating this data to the clinical history of the patients. Researchers plan to determine the clinical significance of the data and to study a larger patient population well defined with regard to implants and autoimmune disease symptoms.

Complement Activation

Key words: complement activation, cellulose acetate, dialysis, sepharose, protein-A, perfusion, research, standards.

The term complement describes a series of serum proteins involved in mediating immune reactions. Complement activation is a tightly regulated process which, in addition to direct cell cytolysis, can have profound affects on the immune, vascular, and coagulation systems. Though complement activation is an important defense mechanism of the host, particularly against microbial infections, inappropriate activation (such as by implanted or external medical devices which encounter human blood) may result in serious acute or chronic reactions.

Examples of devices whose materials might activate complement include perfusion devices, columns for treating blood externally, indwelling artificial vascular grafts, encapsulated drugs or cells, and vascular shunts. At the request of ODE, OST is conducting research to acquire baseline information needed, in particular, for industry standards concerning testing of materials to be used in blood-contacting devices.

A microassay was developed for assaying whole-complement depletion by solid materials used in the construction of blood-contacting medical devices. This method has been submitted as a draft Standard Practice to the ASTM Committee F-4 on Medical and Surgical Materials and Devices via Subcommittee F04.16 on Biocompatibility. Cellulose acetate fibers and powders used in the manufacture of dialysis membranes were tested using this standard practice. Although cellulose powder potently activated complement (57% reduction from control levels when exposed to an equal volume of serum for 1 hour at 37oC), there was no difference between molecular weight 50,000 versus 30,000. Cellulose acetate fibers were less potent than the precursor powders (only 19% reduction from control levels), though storage time (from dates of manufacture) did not produce significant differences between the fibers (9/96 versus 2/89.) These results suggest that adverse patient reactions to dialysis by materials could be related to complement activation, which might not be influenced by molecular weight or age of degradation particles.

Sepharose is used to immobilize protein-A in perfusion columns for removing antibodies from patient blood. Both raw sepharose and sepharose-conjugated protein-A were tested for whole complement depletion. Both resulted in a 75% or greater reduction in whole complement activity versus controls. No significant difference was seen between raw sepharose and sepharose-conjugated protein-A, indicating that the majority of the complement activation was due to the matrix, rather than to the attached protein-A. The activation of complement by sepharose was by the alternative pathway (as documented by Bb generation), rather than by the classical pathway (documented by lack of C4d generation). Washing the sepharose with citrate buffers (used in preparing columns for patient blood) resulted in a temporary blockage of complement activation that was rapidly lost upon sequential exposure to additional serum aliquots. These results indicate the potential for complement activation to be a hazard and/or confounding systemic modifier in therapeutic use of antibody-depleting columns.

Particulate Effects on Immunologic Function

Key words: particles, cytokines, wear and degradation, macrophages, standards, research

Wear and corrosion of implanted medical devices, such as dental and orthopedic prostheses, may produce particulate debris which may lead to acute and chronic inflammatory responses in the host. In addition, polymeric particles, such as polytetrafluoroethylene (PTFE), may be injected directly into the patients for clinical indications. When particulates are present, the host monocytes/macrophages are activated and they synthesize or secrete mediators of inflammation, and phagocytize particles. In order to understand the mechanisms underlying the host immune response to particulates and device-associated infections, OST scientists have focused their studies on the impact of these particulates on macrophage function. Macrophages play a pivotal role in the body’s response to foreign bodies and they also interact with other cellular components in the immune system. OST developed an in vitro assay using established murine macrophages. This assay system was incorporated into an ASTM standard on the Biological Responses to Particles (F04.16.01). The inflammatory potential of particles prepared from medical device materials, such as PTFE, titanium oxide, hydroxyapatite (HA), polymethylmethacrylate (PMMA), SiO2 and fumed silica, polystyrene (PS), CdCl2, CdO, Al2O3 , and diamond particle was studied.

In the in vitro assay, murine macrophage cells were exposed to particles or chemicals with and without bacterial lipopolysaccharide (LPS), which is a component of bacterial cell walls that mimics bacterial infections. The cells were then evaluated for cytotoxicity, production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-a ) and interleukin-6 (IL-6), both inflammatory cytokines. NO is induced by LPS and is critically important in eradicating microorganisms associated with infections, but it can also be harmful by causing tissue injury and vascular collapse. OST studies showed that minute amounts of LPS, which could be associated with a bacterial infection at the site of an implanted device, induced a significant amount of TNF-a , IL-6 and NO production by macrophages.

The in vitro studies showed that TNF-a was induced by PTFE, PMMA, TiO2, HA, SiO2, both forms of cadmium, and Al2O3 particles and by LPS. Polystyrene alone did not stimulate activity. PS in combination with LPS stimulated no activity significantly above the levels in response to LPS alone. Addition of particles to the macrophages did not stimulate NO production. However, addition of LPS to the particles affected the NO production. NO production increased in a dose-response manner with LPS plus PMMA, increased but not in a dose-dependent response with HA, and was inhibited by increasing concentrations of TiO2. Polystyrene particles in combination with LPS produced minimal and variable differences of NO compared to LPS alone.

The in vitro system showed that IL-6 is stimulated by LPS. Neither Al2O3 nor PS alone stimulated IL-6 production. IL-6 production was stimulated by Al2O3 in combination with LPS, but PS in combination with LPS did not stimulate above the LPS alone level.

..

Thus far, the OST studies indicate the following: 1) this in vitro system measuring TNF-a , IL-6 and NO responses can detect differences in biological responses to particles; 2) no particle tested by OST thus far has induced NO whereas LPS is a potent stimulator; 3) some particles stimulate TNF-a production and some do not; 4) some particles enhance, some inhibit, and some have no effect on the stimulation of TNF-a and NO by macrophages in response to LPS; and 5) PS particles may serve as a negative control for evaluating the induction of these three biological responses.

Decontaminating Particles Exposed to Bacterial Lipopolysaccharde

Key words: particles, lipopolysaccharide, nitric oxide, macrophage, research

The presence of lipopolysaccharide (LPS) or endotoxin associated with implanted medical devices can stimulate fever in the host. Manufacturers must submit evidence that their sterilized implanted devices are below a given endotoxin level. The most commonly used assay to test for the presence of endotoxin is the Limulus Amebocyte Lysate (LAL) test. OST scientists have observed, using an in vitro murine macrophage assay, that LPS stimulates nitric oxide (NO) production. Clean, sterilized medical device particles examined thus far do not stimulate NO production, but certain particles that are contaminated with minute amounts of lipopolysaccharide (LPS, endotoxin) do stimulate NO production. Polymethylmethacrylate (PMMA) particles deliberately contaminated with minute amounts of LPS were assayed for the production of NO in the murine macrophage cell system. Treating particles deliberately contaminated with LPS with 70% ethanol at room temperature or higher for more than 24 hours followed by washing three times with endotoxin-free phosphate buffered saline reduced the level of detection of LPS in the in vitro cell system. LPS treated with 70% ethanol also did not stimulate NO production. Both the LAL test and the lack of LPS stimulation of NO production by murine macrophages show that 70% ethanol can inactivate LPS and may be a method to remove LPS from particles that are being tested for inflammatory potential.

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]



Darling Dede:

Thank you for all of this great information. Bless your heart, because you are having family problems, and you continue to help us. These pictures are enough to make most people sick; however, many of the older women in our group have seen these before. You are helping the young women who might be looking at our site to get information before they have these devices implanted into their bodies.

Honey, it is so sad about your daughter, and she should have been sent to rehab...not jail. We will all try to help you to get through this. I have a daughter who has been an alcoholic for many years, and she has gone to rehab, but she comes home and starts to drink and do major drugs again. My older son told us that she is having very bad seizures, and cannot drink anymore. We had to ban her from our lives 20 years ago, because she would not get help. She would abuse me, and call in the middle of the night to ask for money. We can only pray that she will get some help. Her husband runs Dial A Bottle and he is an enabler, and he came from a good home too. They all blame the divorce for most all of their problems, but I wish that they would blame their father for the divorce...he was the one who was causing the problems.

Honey, I just feel like we have failed, and yet we have not failed, they have failed us.

We love you, and wish you the best....Lea and Superman

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Breast Implants part 3

necrosis from silicone rupture

another breast with necrosis from implants

Implants are porous, and fluids flow in and out of them, creating

toxic soup. This goes for saline as well as silicone ! How quickly one

becomes ill from them depends on how good their immune system

is handelling all the toxins. Many get very ill, and dont realize that

it is because the implants have compromised the immune system.

Implant chemicals kill your NK cells, the ones that fight cancer.

Many of us have had several bouts of cancer. I am one of them.

I have had cervical, and colon.

Saline has a shelf life of 2 years. The Saline implants have valves

where they fill them up. These valves can be faulty and can have

bi-directional flow problems where fluids flow freely in and out of them.

http://www.fda.gov/cdrh/ost/reports/fy98/IMMUNOTOX.HTM

If you will read on the FDA site, you will find, under immuno toxicology

the truth about how implants disrupt the endocrin system as well as other things. It is NOT anywhere near where breast implants are, I guess the FDA didnt want people to make the connection......they are protecting

large corporation, and NOT the people ! ! !

Below is parts of the FDA article:

Endocrine Disruption by Medical Device Materials

Key words: estrogen disruption, uterotrophic assay, heat shock proteins, bisphenol A

CDRH is concerned with the potential for certain medical device materials to mimic or interfere with endogenous hormone actions. Because the hormone estrogen is a potent molecule having profound effects at remarkably low doses, assays are needed to assess the potential for harm from materials that may induce unwanted effects due to interference with normal estrogen homeostasis. OST scientists are collaborating with researchers at the Department of Biology, Washington University, on projects focused on improving the use of a key biomarker of exposure to estrogenic compounds and determining the characteristics of the estrogenic activity of bisphenol A, a plasticizer found in some medical devices.

OST scientists are modifying and enhancing the traditional assay for estrogenic effects. The traditional assay utilizes the ability of estrogen to cause a hypertrophy of the uterus in ovariectomized or immature female mice. The purpose of these modifications is to provide mechanistic information that will reduce the number of uncertainties in assessing risk from exposure to estrogenic materials. OST scientists are developing an assay that promises to do just that: obtain mechanistic information while examining estrogenic responses in the whole animal. This is accomplished by a side-by-side comparison of the traditional uterotrophic assay and a specific cellular event, the induction of stress proteins, that occurs when estrogen or estrogen-mimicking materials bind to its specific cellular receptor.

Stress, or heat shock, proteins are synthesized rapidly by most cells in response to various chemical and physical stressors, especially heat. This response is thought to serve a cellular protective function. Other functions have been found, and heat shock proteins are called "chaperones" because they appear to associate with other proteins and hold them in proper conformations. This appears to be their function in relation to steroid hormone receptors: they appear to hold the receptor molecule in an open position, so that the receptor can bind to ligand easily. When the ligand binds, the heat shock protein dissociates; the receptor is free to assume a new shape, one that retains the bound ligand but which also enables the receptor to bind the correct sequence on the genomic DNA, called the hormone responsive element. Thus, OST has tried to identify changes in heat shock proteins as a marker of estrogen receptor binding in tissues from whole animals treated with estrogens.

OST scientists have shown that such changes can be detected in a number of heat shock proteins in the uterus in response to estrogen and that the response is specific to uterine and estrogenic compounds. The effect of exposure time on changes in heat shock proteins was assessed in ovariectomized mice treated with estradiol, the primary estrogen form in the body. Increased relative uterus weight increased linearly between the 4-hour , 8-hour, and 12-hour post-exposure time points, and remained for 1 and 2 days. The histopathology of the uterine lining showed a similar pattern. Changes in the pattern of heat shock protein expression were observed between 6 and 12 hours post-treatment. Thus all three endpoints examined appear at approximately the same time after treatment. This is consistent with the idea that the heat shock protein changes are related specifically to the estradiol effects.

Other steroid and steroid-like compounds were used in order to examine the specificity of the response. The compounds included an androgen, an androgen-receptor antagonist, a progestin, and a partial estrogen. These compounds induced changes in heat shock protein expression, but did not induce uterine swelling. This result demonstrates that the heat shock protein changes are not the result of the stresses to the cells caused by uterine swelling, and the heat shock response may be more sensitive than the uterine response. Compound ICI 182,780, a potent anti-estrogen, had no effect on uterine weights and did not induce changes in heat shock proteins. However, the highest dose of the ICI compound blocked the uterine and heat shock protein effects of co-administered estradiol. Thus heat shock protein induction: 1) is an estrogenic effect independent of uterine swelling; and 2) is a more sensitive indicator of estrogenic effect than is uterine swelling. The histological changes occur in parallel with the uterine swelling effects.

The three endpoints (uterine hypertrophy, histology, and stress protein expression, were used to examine the estrogenic response of the plasticizer bisphenol A. Bisphenol A was determined to be less estrogenic that estradiol (by more than 1000-fold), but caused similar effects. Histological changes in the uterine epithelia were observed at doses 40-fold lower than doses that caused uterine swelling. Although responses were variable, heat shock protein induction was also more sensitive than the uterotrophic response.

Immunological Responses to Silicone Breast Implants

Key words: autoantibodies, silicone breast implants, immunopathology

The breast implant experiments were accomplished in two parts: first to demonstrate immune responses to silicone gel implants in an animal model; and second, to apply the experimental protocols to samples from women with/without breast implants. The objective of these studies was to determine which autoimmune-like symptoms and other symptoms are associated with implanted materials.

OST has developed a rat model to study and understand immune responses to silicone gel and oil used in breast implants. This model included normal rats and a strain of autoimmune rats, that mimicked clinical conditions found in patients with silicone gel breast implants. Mixtures of silicone gel/oil were injected into the mammary area of female rats. Scientists then measured the levels of autoantibodies to collagen and to nuclear proteins developed over 2 years in response to these mixtures.

Results from the rat model indicate that specific autoantibodies may be induced by certain biomaterials. The immune system recognizes a biomaterial-connective tissue protein association as altered-self or as foreign. OST scientists have demonstrated that medical grade silicone oil can stimulate serum autoantibodies against collagen and against DNA when this oil is injected into mammary tissues of rats. Autoantibody production against connective tissue proteins is an immune response that is consistent with reports from women with silicone breast implants. The results also demonstrated pathological changes in animals that may result from the autoimmune response and that silicone gel can migrate to distant anatomical sites or localize at the implantation site. This work has been presented at The FDA Science Forum, The American Association of Immunology, and The American Association of Biochemistry and Molecular Biology.

The implication from these findings is that leaked oil from a breast implant via leaching or with rupture might provide stimulus for the production of autoantibodies in clinical patients. Therefore, OST scientists evaluated autoantibody levels (in blinded experiments) in serum samples from 150 patients representing four groups: women with silicone implants without connective tissue disease, women with silicone implants with connective tissue disease (CTD), women with connective disease but no implants, and healthy women volunteers. Results from these experiments show in a statistically significant manner that elevated autoantibodies to collagen type I, collagen type II and anti-DNA were detected in serum of patients with CTD, CTD + silicone implants, and silicone implants without CTD.

Using two different assays, autoantibodies to connective tissue proteins (e.g., collagen) and to DNA and intranuclear proteins have been detected in women with silicone breast implants. Historically, there is a strong correlation between anti-nuclear antibodies and clinical symptoms of some autoimmune diseases. OST has documented serum immune responses in these patients with the goal of enhancing the ability to predict the likelihood of immunotoxic symptoms occurring in the presence of implants, including breast prostheses. This work has been presented to the Institute of Medicine.

OST scientists are continuing to investigate these results by correlating this data to the clinical history of the patients. Researchers plan to determine the clinical significance of the data and to study a larger patient population well defined with regard to implants and autoimmune disease symptoms.

Complement Activation

Key words: complement activation, cellulose acetate, dialysis, sepharose, protein-A, perfusion, research, standards.

The term complement describes a series of serum proteins involved in mediating immune reactions. Complement activation is a tightly regulated process which, in addition to direct cell cytolysis, can have profound affects on the immune, vascular, and coagulation systems. Though complement activation is an important defense mechanism of the host, particularly against microbial infections, inappropriate activation (such as by implanted or external medical devices which encounter human blood) may result in serious acute or chronic reactions.

Examples of devices whose materials might activate complement include perfusion devices, columns for treating blood externally, indwelling artificial vascular grafts, encapsulated drugs or cells, and vascular shunts. At the request of ODE, OST is conducting research to acquire baseline information needed, in particular, for industry standards concerning testing of materials to be used in blood-contacting devices.

A microassay was developed for assaying whole-complement depletion by solid materials used in the construction of blood-contacting medical devices. This method has been submitted as a draft Standard Practice to the ASTM Committee F-4 on Medical and Surgical Materials and Devices via Subcommittee F04.16 on Biocompatibility. Cellulose acetate fibers and powders used in the manufacture of dialysis membranes were tested using this standard practice. Although cellulose powder potently activated complement (57% reduction from control levels when exposed to an equal volume of serum for 1 hour at 37oC), there was no difference between molecular weight 50,000 versus 30,000. Cellulose acetate fibers were less potent than the precursor powders (only 19% reduction from control levels), though storage time (from dates of manufacture) did not produce significant differences between the fibers (9/96 versus 2/89.) These results suggest that adverse patient reactions to dialysis by materials could be related to complement activation, which might not be influenced by molecular weight or age of degradation particles.

Sepharose is used to immobilize protein-A in perfusion columns for removing antibodies from patient blood. Both raw sepharose and sepharose-conjugated protein-A were tested for whole complement depletion. Both resulted in a 75% or greater reduction in whole complement activity versus controls. No significant difference was seen between raw sepharose and sepharose-conjugated protein-A, indicating that the majority of the complement activation was due to the matrix, rather than to the attached protein-A. The activation of complement by sepharose was by the alternative pathway (as documented by Bb generation), rather than by the classical pathway (documented by lack of C4d generation). Washing the sepharose with citrate buffers (used in preparing columns for patient blood) resulted in a temporary blockage of complement activation that was rapidly lost upon sequential exposure to additional serum aliquots. These results indicate the potential for complement activation to be a hazard and/or confounding systemic modifier in therapeutic use of antibody-depleting columns.

Particulate Effects on Immunologic Function

Key words: particles, cytokines, wear and degradation, macrophages, standards, research

Wear and corrosion of implanted medical devices, such as dental and orthopedic prostheses, may produce particulate debris which may lead to acute and chronic inflammatory responses in the host. In addition, polymeric particles, such as polytetrafluoroethylene (PTFE), may be injected directly into the patients for clinical indications. When particulates are present, the host monocytes/macrophages are activated and they synthesize or secrete mediators of inflammation, and phagocytize particles. In order to understand the mechanisms underlying the host immune response to particulates and device-associated infections, OST scientists have focused their studies on the impact of these particulates on macrophage function. Macrophages play a pivotal role in the body’s response to foreign bodies and they also interact with other cellular components in the immune system. OST developed an in vitro assay using established murine macrophages. This assay system was incorporated into an ASTM standard on the Biological Responses to Particles (F04.16.01). The inflammatory potential of particles prepared from medical device materials, such as PTFE, titanium oxide, hydroxyapatite (HA), polymethylmethacrylate (PMMA), SiO2 and fumed silica, polystyrene (PS), CdCl2, CdO, Al2O3 , and diamond particle was studied.

In the in vitro assay, murine macrophage cells were exposed to particles or chemicals with and without bacterial lipopolysaccharide (LPS), which is a component of bacterial cell walls that mimics bacterial infections. The cells were then evaluated for cytotoxicity, production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-a ) and interleukin-6 (IL-6), both inflammatory cytokines. NO is induced by LPS and is critically important in eradicating microorganisms associated with infections, but it can also be harmful by causing tissue injury and vascular collapse. OST studies showed that minute amounts of LPS, which could be associated with a bacterial infection at the site of an implanted device, induced a significant amount of TNF-a , IL-6 and NO production by macrophages.

The in vitro studies showed that TNF-a was induced by PTFE, PMMA, TiO2, HA, SiO2, both forms of cadmium, and Al2O3 particles and by LPS. Polystyrene alone did not stimulate activity. PS in combination with LPS stimulated no activity significantly above the levels in response to LPS alone. Addition of particles to the macrophages did not stimulate NO production. However, addition of LPS to the particles affected the NO production. NO production increased in a dose-response manner with LPS plus PMMA, increased but not in a dose-dependent response with HA, and was inhibited by increasing concentrations of TiO2. Polystyrene particles in combination with LPS produced minimal and variable differences of NO compared to LPS alone.

The in vitro system showed that IL-6 is stimulated by LPS. Neither Al2O3 nor PS alone stimulated IL-6 production. IL-6 production was stimulated by Al2O3 in combination with LPS, but PS in combination with LPS did not stimulate above the LPS alone level.

..

Thus far, the OST studies indicate the following: 1) this in vitro system measuring TNF-a , IL-6 and NO responses can detect differences in biological responses to particles; 2) no particle tested by OST thus far has induced NO whereas LPS is a potent stimulator; 3) some particles stimulate TNF-a production and some do not; 4) some particles enhance, some inhibit, and some have no effect on the stimulation of TNF-a and NO by macrophages in response to LPS; and 5) PS particles may serve as a negative control for evaluating the induction of these three biological responses.

Decontaminating Particles Exposed to Bacterial Lipopolysaccharde

Key words: particles, lipopolysaccharide, nitric oxide, macrophage, research

The presence of lipopolysaccharide (LPS) or endotoxin associated with implanted medical devices can stimulate fever in the host. Manufacturers must submit evidence that their sterilized implanted devices are below a given endotoxin level. The most commonly used assay to test for the presence of endotoxin is the Limulus Amebocyte Lysate (LAL) test. OST scientists have observed, using an in vitro murine macrophage assay, that LPS stimulates nitric oxide (NO) production. Clean, sterilized medical device particles examined thus far do not stimulate NO production, but certain particles that are contaminated with minute amounts of lipopolysaccharide (LPS, endotoxin) do stimulate NO production. Polymethylmethacrylate (PMMA) particles deliberately contaminated with minute amounts of LPS were assayed for the production of NO in the murine macrophage cell system. Treating particles deliberately contaminated with LPS with 70% ethanol at room temperature or higher for more than 24 hours followed by washing three times with endotoxin-free phosphate buffered saline reduced the level of detection of LPS in the in vitro cell system. LPS treated with 70% ethanol also did not stimulate NO production. Both the LAL test and the lack of LPS stimulation of NO production by murine macrophages show that 70% ethanol can inactivate LPS and may be a method to remove LPS from particles that are being tested for inflammatory potential.

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]

~

You have now gotten rid of your nasty implants

and scar caps, you have been detoxing for years

now, and I believe that replinishing your body with

what it needs with live foods and balancing your body

flora will give it what it needs to build your cells to

strong healthy ones. I think you will be ok.

See, I never detoxed the silicone from my rupture. I

couldnt afford to go to Dr Rays in Dallas to detox,

and I didnt know how to detox at home. I worked

and was a single mom of 2 and didnt have resources

or info.

I do believe with all you have done, and how well you

take care of your "palace" the earthly home for your soul

that God gave you, that you have no worries !

Love and Faith ~ DedeIt's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]

~

You have now gotten rid of your nasty implants

and scar caps, you have been detoxing for years

now, and I believe that replinishing your body with

what it needs with live foods and balancing your body

flora will give it what it needs to build your cells to

strong healthy ones. I think you will be ok.

See, I never detoxed the silicone from my rupture. I

couldnt afford to go to Dr Rays in Dallas to detox,

and I didnt know how to detox at home. I worked

and was a single mom of 2 and didnt have resources

or info.

I do believe with all you have done, and how well you

take care of your "palace" the earthly home for your soul

that God gave you, that you have no worries !

Love and Faith ~ DedeIt's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]

Dede,

Oh Thank you for your message.....I know you have been

going through a lot Dede....I pray you and your daughter

get through this with flying colors.

I really needed that this morning. I have not been

sleeping much and really am trying all sorts of

things right now. Trying not to use meds of course.

Love

In a message dated 3/9/2008 9:55:22 A.M. Eastern Daylight Time, DGRAHAMA@... writes:

~

You have now gotten rid of your nasty implants

and scar caps, you have been detoxing for years

now, and I believe that replinishing your body with

what it needs with live foods and balancing your body

flora will give it what it needs to build your cells to

strong healthy ones. I think you will be ok.

See, I never detoxed the silicone from my rupture. I

couldnt afford to go to Dr Rays in Dallas to detox,

and I didnt know how to detox at home. I worked

and was a single mom of 2 and didnt have resources

or info.

I do believe with all you have done, and how well you

take care of your "palace" the earthly home for your soul

that God gave you, that you have no worries !

Love and Faith ~ Dede

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

[Guest guest]

Dede,

Oh Thank you for your message.....I know you have been

going through a lot Dede....I pray you and your daughter

get through this with flying colors.

I really needed that this morning. I have not been

sleeping much and really am trying all sorts of

things right now. Trying not to use meds of course.

Love

In a message dated 3/9/2008 9:55:22 A.M. Eastern Daylight Time, DGRAHAMA@... writes:

~

You have now gotten rid of your nasty implants

and scar caps, you have been detoxing for years

now, and I believe that replinishing your body with

what it needs with live foods and balancing your body

flora will give it what it needs to build your cells to

strong healthy ones. I think you will be ok.

See, I never detoxed the silicone from my rupture. I

couldnt afford to go to Dr Rays in Dallas to detox,

and I didnt know how to detox at home. I worked

and was a single mom of 2 and didnt have resources

or info.

I do believe with all you have done, and how well you

take care of your "palace" the earthly home for your soul

that God gave you, that you have no worries !

Love and Faith ~ Dede

It's Tax Time! Get tips, forms and advice on AOL Money Finance.

It's Tax Time! Get tips, forms and advice on AOL Money Finance.