kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
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It's 3 articles that I chose to put in one thread.
http://www.thelancet.com/journals/lancet/article/PII0140-6736%2890%2993357-U/fulltext
Toothpaste and Crohn’s disease
SIR,-Professor Sullivan’s paper (Nov 3, p 1096) and subsequent correspondence (Dec 1, p 1382) raise important questions about the impermeability or otherwise of the gastrointestinal tract to ingested
particles. We cannot comment on the connection between insoluble
particle uptake and the pathogenesis of Crohn’s disease, but we have
investigated the uptake and fate of sub-micron particles from the
gastrointestinal tract in the rat. Our aim was to fmd out the extent of
uptake, if any, in view of the assumption that the mammalian
gastrointestinal tract is impenetrable to particles. Knowledge of the
uptake of bacterial and viral particles2 via the M-cells of Peyer’s
patches has been accompanied by periodic reports of particulate
"persorption",3-5 but controversy has persisted.
Insoluble polystyrene particles of well-defined diameters in the
range 50 nm to 3 um fed to rats were found to be taken up mainly via
the Peyer’s patches and subsequently transported to the serosa
(figure, a) and thence by the mesenteric lymphatic vessels to lymph
nodes. Particles up to 300 nm are transported into the venous
circulation and reach the liver in small amounts.6 Polystyrene was
chosen because it is non-biodegradable and completely insoluble,
but the work does demonstrate the size dependency of uptake of
Perhaps we should be more concerned about the fate of insoluble
materials in toothpaste and pharmaceuticals which might be taken
chronically, especially since the intestinal permeability patterns in
some disease states such as Crohn’s disease are abnormally high.7
Particle absorption in rat gastrointestinal tract.
(a) (top). frozen section of Peyer’s patch showing 500 nm polystyrene
fluorescent particles traversing from lumen to serosal side after oral dosing.
(b) (middle). mesenteric lymph vessel and connective tissue with 500
nm titanium dioxide particles (as aggregates, arrowed) after oral dosing.
x about 40.)
(c) (bottom) mesenteric lymph node showing lymphatic vessel with
titanium dioxide aggregates (arrowed). ( x about 75.)
SIR,-As Professor Sullivan points out, toothpaste contains a great
variety of inorganic metals and salts, many of which have been
shown in animal experiments to produce granulomatous lesions in
the intestine. However, the claim that these substances have not
been positively identified in human intestine is incorrect. Scanning
electronmicroscopy and X-ray energy spectroscopyl have revealed
aluminium, silicon, and titanium in Peyer’s patch macrophages in
the terminal ileum of patients with Crohn’s disease and controls; it
has been suggested that since both aluminium and titanium produce
granulomatous lesions in the human lung, these metals may be
involved in the pathogenesis of Crohn’s disease.2 The macrophage,
as the major cell type in intestinal granulomas, has been strongly
implicated in the pathogenesis of Crohn’s disease.3 It seems likely
that metal-containing macrophages will not function normally;
toxic metals such as lead, chromium, and nickel disturb a variety of
macrophage functions, including phagocytosis and enzyme
secretion.4 While Coffey was probably correct in assuming that
these substances are most commonly derived from the diets many of
these metals are on the surface of suture materials. Perhaps the
biological activity of these substances at surgical suture lines
contributes to the high rate of anastomotic recurrence after
operative treatment of Crohn’s disease that we had found
(unpublished).
SIR,-Professor Sullivan invites us to revisit the hypothesis that
toothpaste caused Crohn’s disease. He suggests several possible
explanations for epidemiological findings in Crohn’s disease that
might be explained by toothpaste consumption. Crohn’s disease is
commoner among smokers than non-smokers and he suggests that
smokers consume more toothpaste by brushing more often.
Surveys of oral cleanliness and periodontal disease, however,
indicate that smokers have far worse disease and oral hygiene and
more debris and calculus than non-smokers. Secondly although
people with Crohn’s consume more sugar, sugar consumption is
associated with less regular toothbrushing rather than more.2 The
finding of more Crohn’s disease among white-collar workers is supported by increased brushing activity in this social group, but is
such a non-specific marker of affluence, education, diet, and social
behaviour as to provide little useful insight into the true causal
factor.
SIR,-Professor Sullivan postulates involvement of inorganic
particles from toothpaste in Crohn’s disease. Intestinal mucosal
infiltration by phagocytes, polymorphs, and macrophages1 and the
generation of free radical and related oxygen-derived reactive
metabolites in inflammatory bowel disease2 are associated with an
enhanced blood neutrophil chemiluminescent response.3 The
success of elemental diets in Crohn’s disease, thought to be due to
the elimination of dietary antigens is consistent with the removal of
inorganic particulate toxins from the diet. Various inorganic
particulates that include model aluminosilicates are capable of
stimulating the production of polymorph-derived free radical
oxidants.5 Soluble components of toothpaste could exert a similar
effect. Fluoride may promote the inappropriate and chronic cellular
activation of NADPH oxidase 6leading to the enhanced production
of superoxide and other oxidant tissue-injurious chemical species;
and foaming agents may also contribute to cell membrane
perturbations and activation of the phagocyte respiratory burst.7
Further investigation of the therapeutic use of antioxidant agents,
micronutrient vitamins, and trace elements, as has been suggested
for the pneumoconioses,8 may be of value in Crohn’s disease too.
http://onlinelibrary.wiley.com/doi/10.1097/00054725-200411000-00022/pdf
Bacterial-Metal Interactions: The Potential Role of Aluminum
and Other Trace Elements in the Etiology of Chrohn’s Disease
Despite the recent burst of excitement about the genomics of Crohn’s disease, the critical importance of environmental factors in this condition has been recognized ever since the disease was described. The chief suspects for this role have always been microorganisms and dietary constituents. any candidate microorganisms have been proposed, evaluated and discarded over the decades, but the most persistent theories have revolved around mycobacterial infection.
In sum, we propose that the iron-related trace element uptake and/or regulatory system of either the putative mycobacteria or of the human host, or both, are involved in the pathogenesis of Crohn’s disease. We further propose that the iron-uptake/regulatory system allows access to mycobacteria of metal ions other than iron (especially aluminum) resulting in
an alteration in the organism’s virulence and/or the host’s ability to contain it.
Once the aluminum-loaded organism is incorporated into the host, aluminum enhances the organism’s ability to induce a prominent granulomatous immune response, thus giving rise to the pathologic features of the disease. The implications of such a hypothesis, of course, extend well beyond Crohn’s disease alone.
Over the past twenty years, it has been demonstrated that microbial organisms can sur-vive—indeed, in some instances flourish—under extreme environmental conditions, such as extremes of temperature, high
and low pH, or high concentrations of trace metals and other
potentially toxic substances. Bacterial organisms have a remarkable
capacity to evolve and adapt successfully to such
harsh conditions.
Our hypothesis is testable in both human specimens and
analogous naturally occurring animal disorders as well as in
experimental animals. For example, this concept could be explored
in Johne’s disease, a focally endemic disorder of sheep
with many similarities to Crohn’s disease. Further, experimental
infection by aluminum-enhanced microbial species might
be employed as means for developing new animal models of
Crohn’s disease. Finally, genetic testing in Crohn’s disease patients
for host-related metal ion-dependent functions might
also prove a fruitful avenue of research.
To examine the hypothesis further we have correlated estimated
toothpaste consumption per person in 19854 with mortality data
from 1950-84 (fourteen countries) and incidence from published
studies for 1970-79 (eleven countries).5 The Spearman correlation
coefficient was 0-19 (p=0-52) with mortality and 0-33 (p=0’33)
with incidence. The incidence figure is artifactually raised due to the
clustering of three countries (Italy, France, and Canada, with both
low consumption of toothpaste and low incidence rates of Crohn’s
disease, see figure). If these countries are excluded the correlation
with incidence is, paradoxically - 0-69 (p = 0-06). We were unable
to obtain consumption data for an earlier time period or data on time
trends in consumption, which would have been more appropriate
for examining the association, but it is reasonable to suppose that the
rank ordering for each country has not changed too much over the
past 20-30 years. Although one must be cautious when interpreting
ecological data, our results, as well as the other above-mentioned
studies, do not seem to support the relation between toothpaste
consumption and Crohn’s disease.
http://gut.bmj.com/content/39/2/231.full.pdf
Absence of skin sensitivity to oxides of aluminium,
Silicon, titanium or zirconium in patients with
Crohn's disease
As the alimentary tract is exposed continually
to ingested substances, the possibility
that one or more of these is responsible for CD
is plausible. Dark pigment containing metal
particles in the bowel wall are found in
macrophages within Peyer's patches, which
mediate sampling and processing of inert
particles from the lumen of the bowel.
Experiments in animals have shown that insoluble
polystyrene particles of 50 nm to 3 ,um
are taken up mainly by Peyer's patches, transported
to the serosa, and thence by mesenteric
lymphatic vessels to lymph nodes14; particles of
titanium 500 nm in diameter are handled
similarly. There is some evidence to suggest
that intestinal permeability is increased among
CD patients and their healthy relatives,
suggesting this could be an important initiating
factor in the pathogenesis of CD.15
The results of our study do not suggest that
specific skin sensitivity to the three metals
compounds tested or to silica is present in CD
patients. As skin biopsy is invasive we did not
test further patients in this pilot study.
The presence of metallic particles within
diseased bowel wall most probably results from
intestinal absorption, but without pathological
consequence, as it also occurs in health.
http://www.thelancet.com/journals/lancet/article/PII0140-6736%2890%2993357-U/fulltext
Toothpaste and Crohn’s disease
SIR,-Professor Sullivan’s paper (Nov 3, p 1096) and subsequent correspondence (Dec 1, p 1382) raise important questions about the impermeability or otherwise of the gastrointestinal tract to ingested
particles. We cannot comment on the connection between insoluble
particle uptake and the pathogenesis of Crohn’s disease, but we have
investigated the uptake and fate of sub-micron particles from the
gastrointestinal tract in the rat. Our aim was to fmd out the extent of
uptake, if any, in view of the assumption that the mammalian
gastrointestinal tract is impenetrable to particles. Knowledge of the
uptake of bacterial and viral particles2 via the M-cells of Peyer’s
patches has been accompanied by periodic reports of particulate
"persorption",3-5 but controversy has persisted.
Insoluble polystyrene particles of well-defined diameters in the
range 50 nm to 3 um fed to rats were found to be taken up mainly via
the Peyer’s patches and subsequently transported to the serosa
(figure, a) and thence by the mesenteric lymphatic vessels to lymph
nodes. Particles up to 300 nm are transported into the venous
circulation and reach the liver in small amounts.6 Polystyrene was
chosen because it is non-biodegradable and completely insoluble,
but the work does demonstrate the size dependency of uptake of
Perhaps we should be more concerned about the fate of insoluble
materials in toothpaste and pharmaceuticals which might be taken
chronically, especially since the intestinal permeability patterns in
some disease states such as Crohn’s disease are abnormally high.7
Particle absorption in rat gastrointestinal tract.
(a) (top). frozen section of Peyer’s patch showing 500 nm polystyrene
fluorescent particles traversing from lumen to serosal side after oral dosing.
(b) (middle). mesenteric lymph vessel and connective tissue with 500
nm titanium dioxide particles (as aggregates, arrowed) after oral dosing.
x about 40.)
(c) (bottom) mesenteric lymph node showing lymphatic vessel with
titanium dioxide aggregates (arrowed). ( x about 75.)
SIR,-As Professor Sullivan points out, toothpaste contains a great
variety of inorganic metals and salts, many of which have been
shown in animal experiments to produce granulomatous lesions in
the intestine. However, the claim that these substances have not
been positively identified in human intestine is incorrect. Scanning
electronmicroscopy and X-ray energy spectroscopyl have revealed
aluminium, silicon, and titanium in Peyer’s patch macrophages in
the terminal ileum of patients with Crohn’s disease and controls; it
has been suggested that since both aluminium and titanium produce
granulomatous lesions in the human lung, these metals may be
involved in the pathogenesis of Crohn’s disease.2 The macrophage,
as the major cell type in intestinal granulomas, has been strongly
implicated in the pathogenesis of Crohn’s disease.3 It seems likely
that metal-containing macrophages will not function normally;
toxic metals such as lead, chromium, and nickel disturb a variety of
macrophage functions, including phagocytosis and enzyme
secretion.4 While Coffey was probably correct in assuming that
these substances are most commonly derived from the diets many of
these metals are on the surface of suture materials. Perhaps the
biological activity of these substances at surgical suture lines
contributes to the high rate of anastomotic recurrence after
operative treatment of Crohn’s disease that we had found
(unpublished).
SIR,-Professor Sullivan invites us to revisit the hypothesis that
toothpaste caused Crohn’s disease. He suggests several possible
explanations for epidemiological findings in Crohn’s disease that
might be explained by toothpaste consumption. Crohn’s disease is
commoner among smokers than non-smokers and he suggests that
smokers consume more toothpaste by brushing more often.
Surveys of oral cleanliness and periodontal disease, however,
indicate that smokers have far worse disease and oral hygiene and
more debris and calculus than non-smokers. Secondly although
people with Crohn’s consume more sugar, sugar consumption is
associated with less regular toothbrushing rather than more.2 The
finding of more Crohn’s disease among white-collar workers is supported by increased brushing activity in this social group, but is
such a non-specific marker of affluence, education, diet, and social
behaviour as to provide little useful insight into the true causal
factor.
SIR,-Professor Sullivan postulates involvement of inorganic
particles from toothpaste in Crohn’s disease. Intestinal mucosal
infiltration by phagocytes, polymorphs, and macrophages1 and the
generation of free radical and related oxygen-derived reactive
metabolites in inflammatory bowel disease2 are associated with an
enhanced blood neutrophil chemiluminescent response.3 The
success of elemental diets in Crohn’s disease, thought to be due to
the elimination of dietary antigens is consistent with the removal of
inorganic particulate toxins from the diet. Various inorganic
particulates that include model aluminosilicates are capable of
stimulating the production of polymorph-derived free radical
oxidants.5 Soluble components of toothpaste could exert a similar
effect. Fluoride may promote the inappropriate and chronic cellular
activation of NADPH oxidase 6leading to the enhanced production
of superoxide and other oxidant tissue-injurious chemical species;
and foaming agents may also contribute to cell membrane
perturbations and activation of the phagocyte respiratory burst.7
Further investigation of the therapeutic use of antioxidant agents,
micronutrient vitamins, and trace elements, as has been suggested
for the pneumoconioses,8 may be of value in Crohn’s disease too.
http://onlinelibrary.wiley.com/doi/10.1097/00054725-200411000-00022/pdf
Bacterial-Metal Interactions: The Potential Role of Aluminum
and Other Trace Elements in the Etiology of Chrohn’s Disease
Despite the recent burst of excitement about the genomics of Crohn’s disease, the critical importance of environmental factors in this condition has been recognized ever since the disease was described. The chief suspects for this role have always been microorganisms and dietary constituents. any candidate microorganisms have been proposed, evaluated and discarded over the decades, but the most persistent theories have revolved around mycobacterial infection.
In sum, we propose that the iron-related trace element uptake and/or regulatory system of either the putative mycobacteria or of the human host, or both, are involved in the pathogenesis of Crohn’s disease. We further propose that the iron-uptake/regulatory system allows access to mycobacteria of metal ions other than iron (especially aluminum) resulting in
an alteration in the organism’s virulence and/or the host’s ability to contain it.
Once the aluminum-loaded organism is incorporated into the host, aluminum enhances the organism’s ability to induce a prominent granulomatous immune response, thus giving rise to the pathologic features of the disease. The implications of such a hypothesis, of course, extend well beyond Crohn’s disease alone.
Over the past twenty years, it has been demonstrated that microbial organisms can sur-vive—indeed, in some instances flourish—under extreme environmental conditions, such as extremes of temperature, high
and low pH, or high concentrations of trace metals and other
potentially toxic substances. Bacterial organisms have a remarkable
capacity to evolve and adapt successfully to such
harsh conditions.
Our hypothesis is testable in both human specimens and
analogous naturally occurring animal disorders as well as in
experimental animals. For example, this concept could be explored
in Johne’s disease, a focally endemic disorder of sheep
with many similarities to Crohn’s disease. Further, experimental
infection by aluminum-enhanced microbial species might
be employed as means for developing new animal models of
Crohn’s disease. Finally, genetic testing in Crohn’s disease patients
for host-related metal ion-dependent functions might
also prove a fruitful avenue of research.
To examine the hypothesis further we have correlated estimated
toothpaste consumption per person in 19854 with mortality data
from 1950-84 (fourteen countries) and incidence from published
studies for 1970-79 (eleven countries).5 The Spearman correlation
coefficient was 0-19 (p=0-52) with mortality and 0-33 (p=0’33)
with incidence. The incidence figure is artifactually raised due to the
clustering of three countries (Italy, France, and Canada, with both
low consumption of toothpaste and low incidence rates of Crohn’s
disease, see figure). If these countries are excluded the correlation
with incidence is, paradoxically - 0-69 (p = 0-06). We were unable
to obtain consumption data for an earlier time period or data on time
trends in consumption, which would have been more appropriate
for examining the association, but it is reasonable to suppose that the
rank ordering for each country has not changed too much over the
past 20-30 years. Although one must be cautious when interpreting
ecological data, our results, as well as the other above-mentioned
studies, do not seem to support the relation between toothpaste
consumption and Crohn’s disease.
http://gut.bmj.com/content/39/2/231.full.pdf
Absence of skin sensitivity to oxides of aluminium,
Silicon, titanium or zirconium in patients with
Crohn's disease
As the alimentary tract is exposed continually
to ingested substances, the possibility
that one or more of these is responsible for CD
is plausible. Dark pigment containing metal
particles in the bowel wall are found in
macrophages within Peyer's patches, which
mediate sampling and processing of inert
particles from the lumen of the bowel.
Experiments in animals have shown that insoluble
polystyrene particles of 50 nm to 3 ,um
are taken up mainly by Peyer's patches, transported
to the serosa, and thence by mesenteric
lymphatic vessels to lymph nodes14; particles of
titanium 500 nm in diameter are handled
similarly. There is some evidence to suggest
that intestinal permeability is increased among
CD patients and their healthy relatives,
suggesting this could be an important initiating
factor in the pathogenesis of CD.15
The results of our study do not suggest that
specific skin sensitivity to the three metals
compounds tested or to silica is present in CD
patients. As skin biopsy is invasive we did not
test further patients in this pilot study.
The presence of metallic particles within
diseased bowel wall most probably results from
intestinal absorption, but without pathological
consequence, as it also occurs in health.
