Aspirin: Testimonials, And Questions Answered

[charlie]

Thank you Destiny!

 

[Yves]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

 

[gretchen]

I took 2 yesterday plus 3 right before bed; woke up early around 5:30 (much earlier than I've been getting up lately) and feel pretty good today. I did have to get up and pee in the middle of the night, but that's fairly normal for me. I seem to sleep better in the first half of my cycle.

 

[Destiny]

I decided to take one 325mg aspirin before weight training three times a week, instead of just a baby aspirin. I also take Vit K2 now, 1mg everyday and a second dose when I take one aspirin. I feel better during and especially towards the end of my training session, as in my muscles less stressed and I recuperate easier.

 

[charlie]

Thanks Destiny. I will keep that in mind if I ever start working out again.

 

[charlie]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

I honestly dont know what to say about this. Hope someone else chimes in.

 

[SheilaHelm1]

How long does dispersible aspirin stay 'active for' in a bottle of carbonated water? Would it still be effective after a couple of days?
Reason I ask is I can still taste the aspirin in it but just need to know if I'm wasting my time forcing myself to have it, cos I'm not a big fan of cold fizzy drinks but its more bearable this way.
Thanks for any opinions in advance

 

[gretchen]

I'm wondering if aspirin is doing more harm than good. My breasts are constantly swollen despite also using progesterone. Also sick of the constant ringing in my ears.

 

[chris]

gretchen - Is the aspirin responsible? Have you tried dropping the aspirin for a time? I personally wouldn't continue using something that I didn't think was benefiting me.

 

[gretchen]

gretchen - Is the aspirin responsible? Have you tried dropping the aspirin for a time? I personally wouldn't continue using something that I didn't think was benefiting me.

I dropped it in the fall. I'm enchanted with it though, and will probably continue. It does warm me up and used to work for my estrogen issues(boobs got smaller). I read it has something to do with copper; I didn't add oysters till recently so maybe that's it.

 

[j.]

Are your vitamin K levels good, gretchen? Some people even take vit K supplements when they take aspirin.

 

[gretchen]

Are your vitamin K levels good, gretchen? Some people even take vit K supplements when they take aspirin.

No, it's one of those things I might never buy. Do you take vitamin K?

 

[j.]

Are your vitamin K levels good, gretchen? Some people even take vit K supplements when they take aspirin.

No, it's one of those things I might never buy. Do you take vitamin K?

I don't, but I don't take aspirin either, so it's less important to me.

 

[gretchen]

Are your vitamin K levels good, gretchen? Some people even take vit K supplements when they take aspirin.

No, it's one of those things I might never buy. Do you take vitamin K?

I don't, but I don't take aspirin either, so it's less important to me.

Why no aspirin?

 

[j.]

Why no aspirin?

I just want to try the diet aspects. I haven't read about it enough to make the jump and try the supplements, except vitamin A if I get skin issues.

 

[ah.]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

I do believe this is a serious concern, and would be interested in hearing more thoughts on this from others.

It sounds as though protecting the gut while taking moderate to high doses of aspirin would be strongly advised, though I wonder what the most effective way to do that is, and whether some of the adverse symptoms folks are reporting could be linked to some level of endotoxemia.

 

[nwo2012]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

I do believe this is a serious concern, and would be interested in hearing more thoughts on this from others.

It sounds as though protecting the gut while taking moderate to high doses of aspirin would be strongly advised, though I wonder what the most effective way to do that is, and whether some of the adverse symptoms folks are reporting could be linked to some level of endotoxemia.

Context?
We know that you take aspirin after a meal and dissolved in a glass of warm water. How were the test subjects consuming theirs? Context is very important.

 

[kettlebell]

Why no aspirin?

I just want to try the diet aspects. I haven't read about it enough to make the jump and try the supplements, except vitamin A if I get skin issues.

Totally understand that. But saying that K2 and D if you aren't getting them from diet/sunlight are essential for anyone and everyone.

I swear by Aspirin. It makes a BIG difference in my temperature, heart rate and mood. My ability to tolerate it in higher doses is building too which is interesting.

 

[kettlebell]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

I do believe this is a serious concern, and would be interested in hearing more thoughts on this from others.

It sounds as though protecting the gut while taking moderate to high doses of aspirin would be strongly advised, though I wonder what the most effective way to do that is, and whether some of the adverse symptoms folks are reporting could be linked to some level of endotoxemia.

Context?
We know that you take aspirin after a meal and dissolved in a glass of warm water. How were the test subjects consuming theirs? Context is very important.

Couldn't agree more. I personally believe Aspirin is very safe if you build up slowly - Especially if you take it as nwo2012 mentions, and with the correct amounts of K2. Granted, if you have pre existing stomach or intestine issues you will need to be careful until those issues are sorted out. I have been on between 1-2gm a day depending on requirements day to day for an extended period of time now, always with food and lots of K2 and have had no issues whatsoever but maybe im just lucky!

Even the dosage on the packet for adults is up to tablets (900mg) every 4 hours and "Not more than 4 doses in any 24 hour period" Thats up to 3.6gm every 24 hours. Thats a lot! An over the counter drug would never be recommended in amounts up to that much unless it was a very safe. Sainsubury (Where I got this Aspirin from) certainly would be seting themselves up for some serious litigation otherwise. Every other Aspirin I have seen in the UK has the same recommendation.

 

[nwo2012]

Is anyone concerned about impaired intestinal barrier (i.e leaky gut) with aspirin? Since more leakiness of the bowels increase endotoxin absorption this should be a concern. It would also be ironic since aspirin is beneficial in so many ways against the effects of endotoxin (http://www.ncbi.nlm.nih.gov/pubmed/6894770) Is there an antidote or just a side effect we have to live with?

http://www.ncbi.nlm.nih.gov/pubmed/22377941

http://www.ncbi.nlm.nih.gov/pubmed/18397235

http://www.ncbi.nlm.nih.gov/pubmed/17436199

I do believe this is a serious concern, and would be interested in hearing more thoughts on this from others.

It sounds as though protecting the gut while taking moderate to high doses of aspirin would be strongly advised, though I wonder what the most effective way to do that is, and whether some of the adverse symptoms folks are reporting could be linked to some level of endotoxemia.

Here is Ray's reply:

Those liver guys should know the importance of bacteria in the small intestine (where they shouldn't live) for liver inflammation. Aspirin is not only antiseptic, it protects barrier functions everywhere, partly by decreasing VEGF, the permeability factor.


Cytokine. 2012 Aug;59(2):442-9.
Evaluation of inflammatory and angiogenic factors in patients with non-alcoholic
fatty liver disease.
Coulon S, Francque S, Colle I, Verrijken A, Blomme B, Heindryckx F, De Munter S,
Prawitt J, Caron S, Staels B, Van Vlierberghe H, Van Gaal L, Geerts A.
Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent,
Belgium. [email protected]
The liver is a major target of injury in obese patients. Non-alcoholic fatty
liver disease (NAFLD) is present in 60-90% of obese Americans and can range from
simple steatosis to the more severe non-alcoholic steatohepatitis (NASH). The
onset of a chronic inflammatory reaction marks the progression from simple
steatosis to NASH and the expansion of adipose tissue is strongly associated with
angiogenesis. Therefore, we determined the serum concentration of inflammatory
[tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6)] and angiogenic
[vascular endothelial growth factor A (VEGF)] cytokines and soluble VEGF
receptors 1 and 2 (sVEGFR1, sVEGFR2) in the serum of an obese population with
simple steatosis and NASH compared to healthy controls. Moreover, we determined
the TNFα, IL6, VEGF, VEGFR1 and VEGFR2 gene expression in the liver of these
simple steatosis and NASH patients. The population consisted of 30 obese
patients, which were diagnosed with simple steatosis and 32 patients with NASH
and compared to 30 age-and-sex matched healthy controls. Mean serum TNFα levels
were elevated in the serum of simple steatosis and NASH patients compared to
healthy controls, reaching significance in NASH patients. IL6 was significantly
increased in simple steatosis and NASH patients compared to the healthy controls.
VEGF levels were significantly elevated in patients with simple steatosis and
borderline significantly elevated in NASH patients compared to the serum levels
of healthy control subjects. The concentration of sVEGFR1 was significantly
increased in serum of simple steatosis and NASH patients compared to controls.
sVEGFR2 concentration was not significantly different in the three groups. TNFα
mRNA expression was higher in NASH patients compared to simple steatosis
patients. Hepatic gene expression of VEGF, VEGFR1 and VEGFR2 were slightly
decreased in NASH patients compared to simple steatosis patients. These data
indicate the involvement of inflammatory (TNFα and IL6), angiogenic (VEGF)
cytokines and sVEGFR1 in the pathophysiology of NAFLD.

Lab Invest. 2012 Jan;92(1):9-21. doi: 10.1038/labinvest.2011.122. Epub 2011 Sep 5.
Early endothelial damage and increased colonic vascular permeability in the
development of experimental ulcerative colitis in rats and mice.
Tolstanova G, Deng X, French SW, Lungo W, Paunovic B, Khomenko T, Ahluwalia A,
Kaplan T, Dacosta-Iyer M, Tarnawski A, Szabo S, Sandor Z.
Diagnostic and Molecular Medicine, VA Long Beach Healthcare System, Long Beach,
CA 90822, USA.
The role of endothelial damage and increased vascular permeability (VP) in the
pathogenesis of ulcerative colitis (UC) has not been investigated. We examined
using functional, morphologic, and molecular biologic studies whether and to what
extent the endothelial barrier dysfunction precedes enhanced epithelial
permeability (EP) and the development of mucosal lesions during the early stages
of experimental UC. We showed that in rats with iodoacetamide (IA)-induced UC
increased colonic VP occurs early (ie, 2.6-fold increase at 15 min, P<0.01)
preceding changes in epithelial barrier permeability. EP was unchanged at 15 and
30 min after IA administration and was increased 1.9-fold at 1 h and 6.7-fold at
2 h (both P<0.001) after IA. In the dextran sodium sulfate-induced slowly
developing UC, colonic VP was significantly increased in 2 days (P<0.05) and EP
only in 4 days (P<0.05). Mucosal endothelial injury led to hypoxia (P<0.05) of
colonic surface epithelial cells 30 min after IA administration that was
associated with increased expressions of transcription factors hypoxia-inducible
factor-1α and early growth response-1. Electron and light microscopy demonstrated
areas of colonic mucosa with perivascular edema covered by intact layer of
surface epithelial cells in both rat and mouse models of UC. This is the first
demonstration in four models of UC that endothelial damage, increased colonic VP,
perivascular edema, and epithelial hypoxia precede epithelial barrier dysfunction
that is followed by erosions, ulceration, and inflammation in UC.

J Exp Med. 2006 Jun 12;203(6):1447-58. Epub 2006 May 15.
Vascular endothelial growth factor is an important determinant of sepsis
morbidity and mortality.
Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L,
Belikoff B, Buras J, Simms BT, Mizgerd JP, Carmeliet P, Karumanchi SA, Aird WC.
Center for Vascular Biology Research, Division of Molecular and Vascular
Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Sepsis, the systemic inflammatory response to infection, is a leading cause of
morbidity and mortality. The mechanisms of sepsis pathophysiology remain obscure
but are likely to involve a complex interplay between mediators of the
inflammatory and coagulation pathways. An improved understanding of these
mechanisms should provide an important foundation for developing novel therapies.
In this study, we show that sepsis is associated with a time-dependent increase
in circulating levels of vascular endothelial growth factor (VEGF) and placental
growth factor (PlGF) in animal and human models of sepsis. Adenovirus-mediated
overexpression of soluble Flt-1 (sFlt-1) in a mouse model of endotoxemia
attenuated the rise in VEGF and PlGF levels and blocked the effect of endotoxemia
on cardiac function, vascular permeability, and mortality. Similarly, in a cecal
ligation puncture (CLP) model, adenovirus-sFlt-1 protected against cardiac
dysfunction and mortality. When administered in a therapeutic regimen beginning 1
h after the onset of endotoxemia or CLP, sFlt peptide resulted in marked
improvement in cardiac physiology and survival. Systemic administration of
antibodies against the transmembrane receptor Flk-1 but not Flt-1 protected
against sepsis mortality. Adenovirus-mediated overexpression of VEGF but not PlGF
exacerbated the lipopolysaccharide-mediated toxic effects. Together, these data
support a pathophysiological role for VEGF in mediating the sepsis phenotype.

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9. Epub 2006 Feb 3.
Inhibitors of VEGF receptors-1 and -2 based on the
2-((pyridin-4-yl)ethyl)pyridine template.
Kiselyov AS, Semenova M, Semenov VV, Milligan D.
Small Molecule Drug Discovery, Chemical Diversity, Inc, 11558 Sorrento Valley
Road, San Diego, CA 92121, USA. [email protected]
We have developed a series of novel potent ((pyridin-4-yl)ethyl)pyridine
derivatives active against kinases VEGFR-1 and -2. Both specific and dual
ATP-competitive inhibitors of VEGFR-2 were identified. Kinase selectivity could
be controlled by varying the arylamino substituent at the 1,3,4-oxadiazole ring.
The most specific molecules displayed >10-fold selectivity for VEGFR-2 over
VEGFR-1. Compound activities in vitro and in cell-based assays (IC(50)<100nM)
were similar to those of reported clinical and development candidates, including
PTK787 (Vatalanibtrade mark). High permeability of active compounds across the
Caco-2 cell monolayer (>30x10(-5)cm/min) is indicative of their potential for
intestinal absorption upon oral administration.

Inflammation. 2004 Oct;28(5):271-8.
Vascular endothelial growth factor blockade reduces plasma cytokines in a murine
model of polymicrobial sepsis.
Nolan A, Weiden MD, Thurston G, Gold JA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New
York University School of Medicine, USA.
Numerous cytokines, including vascular endothelial growth factor (VEGF), are
implicated in the pathogenesis of sepsis. While overexpression of VEGF produces
pulmonary capillary leak, the role of VEGF in sepsis is less clear. We
investigated VEGF in sepsis, utilizing a VEGF trap (VEGF(T)). Polymicrobial
sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP) and
resulted in significantly increased plasma VEGF levels (234 vs. 46 pg/mL; p =
0.03). Inhibition of VEGF had no effect on mortality or lung leak but did
attenuate plasma IL-6 (120 vs. 236 ng/mL; p = 0.02) and IL-10 (16 vs. 41 ng/mL; p
= 0.03). These alterations in inflammatory cytokines were associated with
increased levels of the dominant negative inhibitory C/EBPbeta. In vitro, VEGF
stimulated IL-6, IL-10 and reduced the inhibitory isoform of C/EBPbeta in
cultured macrophages. Together these data suggest VEGF can regulate inflammatory
cytokine production in murine polymicrobial sepsis, via regulation of C/EBPbeta.

Dig Dis Sci. 2004 Jan;49(1):109-15.
Vascular endothelial growth factor (VEGF)--a possible mediator of inflammation
and mucosal permeability in patients with collagenous colitis.
Taha Y, Raab Y, Larsson A, Carlson M, Lööf L, Gerdin B, Thörn M.
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
[email protected]
Patients with collagenous colitis have watery diarrhea and histopathologically
thickened collagen layer with discrete signs of mucosal inflammation. Vascular
endothelial growth factor (VEGF) is a potent angiogenic, mitogenic, permeability,
and fibrosis enhancing peptide and it was studied by segmental perfusion and
immunohistochemistry in patients and controls. The concentrations of VEGF were
significantly increased in perfusates from both the descending colon and the
rectum in patients compared to controls but this difference was not found in
serum. Immunohistochemical staining showed expression of VEGF within colon
epithelial cells, inflammatory cells, and fibroblasts in the lamina propria. The
intensity of staining in the surface epithelium was not different between
patients and controls but in the lamina propria the intensity was significantly
higher among controls. Patients with collagenous colitis have increased
colorectal mucosal secretion of VEGF, which may lead to albumin leakage and
promote fibrosis with deposition of collagen.

J Cardiovasc Med (Hagerstown). 2012 Mar;13(3):187-93.
Adherence junction proteins in angiogenesis: modulation by aspirin and salicylic
acid.
Khaidakov M, Mitra S, Mehta JL.
University of Arkansas for Medical Sciences, Department of Internal Medicine, and
the Veterans Affairs Medical Center, Little Rock, Arkansas 72212, USA.
[email protected]
BACKGROUND: The development of neovasculature correlates with plaque instability
and rupture as well as tumor growth and aggressiveness. In recent years, aspirin
has emerged as a powerful modality in prophylaxis of cardiovascular events, which
may be linked to its inhibitory effects on angiogenesis.
METHODS AND RESULTS: We studied the role of endothelial adherens junctions in
angiogenesis and the modulation of adherens junctions by acetylsalicylic acid
(ASA) and salicylic acid as mechanisms of the angiostatic potential of these
agents. Exposure of human umbilical cord endothelial cells (HUVECs) to vascular
endothelial growth factor (VEGF) significantly enhanced tube formation. The
disruption of adherens junctions as well as phosphorylation and cytoplasmic
translocation of VE-cadherin and p120 catenin were early consequences of VEGF
addition to the medium bathing the HUVECs. Pretreatment with ASA and salicylic
acid prevented changes in adherence junction proteins and inhibited VEGF-induced
tube formation by HUVECs in a dose-dependent manner.
CONCLUSION: Angiogenesis is associated with significant alterations in adherens
junctions. Both ASA and salicylic acid reduce angiogenesis by modulating adherens
junctions.

J Cardiovasc Pharmacol. 2012 Aug;60(2):187-92.
Aspirin downregulates angiotensin type 1 receptor transcription implications in
capillary formation from endothelial cells.
Mitra S, Wang X, Khaidakov M, Ding Z, Ayyadevera S, Hearnsberger E, Goyal T,
Mehta JL.
Cardiovascular Division, University of Arkansas for Medical Sciences, Little
Rock, AR 72212, USA.
Aspirin [acetyl salicylic acid (ASA)] inhibits nicotinamide adenine dinucleotide
phosphate (NADPH) oxidase and reactive oxygen species generation, a pathway that
underlies formation of new capillaries (angiogenesis). Angiotensin II (Ang II)
participates in angiogenesis by activating type 1 receptor (AT1R). We examined if
ASA would inhibit AT1R transcription, which requires NADPH oxidase, and thereby
new capillary formation. Human umbilical vein endothelial cells were cultured in
Matrigel and treated with Ang II with and without ASA. Expression of AT1R and
NADPH oxidase was measured by quantitative polymerase chain reaction. Ang II in
low concentrations induced AT1R messenger RNA and new capillary formation. ASA
and its salicylic acid (SA) moiety both suppressed Ang II-mediated AT1R and
vascular endothelial growth factor expression and the subsequent new capillary
formation. Of note, the AT1R blocker losartan prevented new capillary formation.
ASA and SA also suppressed NADPH oxidase (p22, p47, p67, and gp91 messenger RNA)
expression. These observations suggest that ASA can inhibit Ang II-induced
capillary formation in part via blocking NADPH oxidase and AT1R transcription.
Because SA moiety had similar effect as ASA on AT1R expression, we suggest that
the effect of ASA on new capillary formation is mediated by its SA moiety.

Int J Cardiol. 2004 Mar;94(1):25-9.
Aspirin decreases vascular endothelial growth factor release during myocardial
ischemia.
Gerrah R, Fogel M, Gilon D.
Department of Cardiothoracic Surgery, Hadassah University Hospital, P.O.B. 12000,
Jerusalem 91120, Israel. [email protected]
BACKGROUND: Vascular Endothelial Growth Factor (VEGF) is an important
angiogenesis factor involved in pathophysiology of cardiovascular diseases.
Controlling this factor's level in the serum might have significant prognostic
outcomes.
METHODS: Twenty-four patients undergoing coronary artery bypass grafting were
prospectively categorized into two groups according to aspirin administration
before surgery. Vascular Endothelial Growth Factor levels were compared and
correlated and adjusted with platelets count between two groups in the serum,
before and after the surgery. Serum creatine kinase (CK) levels were determined
before and after the operation in parallel to other clinical data.
RESULTS: Vascular Endothelial Growth Factor levels were significantly lower in
patients of the aspirin group compared to those of the non-aspirin group; 94+/-61
vs. 241+/-118 pg/ml, p=0.0003, respectively, this-despite an absence of
difference in the platelet count between the groups. These titers decreased
postoperatively in both groups, 94+/-61 to 10+/-9 pg/ml, p=0.001 in aspirin group
and from 241+/-118 to 84+/-54 pg/ml, p=0.001 in control group. Serum creatine
kinase levels were higher in the non-aspirin group, 214+/-83 u/l compared to
70+/-32 u/l in the aspirin group. Creatine kinase levels increased significantly
postoperatively in both groups; however, the aspirin group had a significantly
lower creatine kinase levels compared to non-aspirin group, 107+/-51 vs.
401+/-127 u/l, respectively, p=<0.0001. A significant correlation was seen
between VEGF levels and platelets count in both groups, r=0.5.
CONCLUSIONS: Aspirin treated patients have lower Vascular Endothelial Growth
Factor titer levels in the perioperative course. This difference between the
aspirin and the non-aspirin group is not accounted for by the platelets count.

Am J Hypertens. 2006 Sep;19(9):970-7; discussion 978.
Effects of aspirin on intra-platelet vascular endothelial growth factor,
angiopoietin-1, and p-selectin levels in hypertensive patients.
Nadar S, Blann AD, Lip GY.
Haemostasis Thrombosis and Vascular Biology Unit, University Department of
Medicine, City Hospital, Birmingham, England.
BACKGROUND: Although aspirin is useful in reducing platelet activation and
cardiovascular events, its effects on platelet levels of angiogenic factors, such
as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), and
markers of platelet activation in hypertension are unknown. The aim of this study
was to study the effects of aspirin on the platelet morphology, plasma and
platelet levels of VEGF (sVEGF and pVEGF respectively), Ang-1 (sAng-1 and pAng-1
respectively), and P-selectin (sPsel and pPsel respectively) in patients with
well controlled hypertension.
METHODS: A total of 35 aspirin-naive, hypertensive patients (29 male and six
female; mean age 64 years) were compared with 30 (23 male, seven female, mean age
59 years) normotensive control subjects. Blood was collected for plasma VEGF,
P-selectin, and Ang-1 (enzyme-linked immunoassay), intra-platelet levels of VEGF,
Ang-1, and P-selectin, and platelet volume and mass. Research indices in
hypertensive patients were studied before and after 3 months treatment with
aspirin 75 mg daily.
RESULTS: Hypertensive patients had significantly higher plasma levels of VEGF
(P=.04), Ang-1 (P<.001), as well as pVEGF (P=.008), pAng-1(P=.001), sPsel
(P=.02), pPsel (P<.001), and mean platelet mass (P=.01) when compared with
control subjects. After treatment with aspirin for 3 months, there were
significant reductions in plasma VEGF (P=.01), pAng-1 (P=.04), sPsel (P=.001),
and pPsel (P<.001) levels, but not levels of platelet VEGF and plasma Ang-1.
Neither pVEGF nor pAng-1 correlated with blood pressure or with their respective
plasma levels.
CONCLUSIONS: The use of aspirin in high-risk hypertensive patients leads to a
reduction in intra-platelet angiogenic growth factors and platelet activation.
This may have implications for the use of aspirin in conditions (such as vascular
disease) that have been associated with an increase in angiogenesis and platelet
activation.

Clin Sci (Lond). 2004 Jan;106(1):83-91.
Aspirin inhibits endothelial nitric oxide synthase (eNOS) and Flk-1 (vascular
endothelial growth factor receptor-2) prior to rat colon tumour development.
Escribano M, Molero L, López-Farré A, Abarrategui C, Carrasco C, García-Mendez A,
Manzarbeitia F, Martín MJ, Vázquez M, Sánchez-Fayos P, Rico L, Porres Cubero JC.
Digestive Research Laboratory, Fundación Jiménez Díaz, Av Reyes Católicos 2,
28040 Madrid, Spain.
Formation of blood vessels is a fundamental element in the control of tumour
growth in which vascular endothelial growth factor (VEGF) and nitric oxide (NO)
have been demonstrated to be involved. Our aim was to analyse whether changes in
the expression of endothelial NO synthase (eNOS) and VEGF in colonic tissue could
be detected early and even before the identification of colon tumour-associated
morphological modifications in azoxymethane-treated rats. We studied further
whether aspirin treatment changed these parameters. An increased expression of
both eNOS and VEGF in colonic tissue from azoxymethane-treated rats compared with
that from control rats was found. Aspirin treatment (10 mg/kg of body weight per
day) reduced eNOS expression, but failed to modify the expression of VEGF in the
colonic tissue of azoxymethane-treated rats. No evidence of aberrant crypt
formation or changes in the number of blood vessels were observed in the colon of
any of the animals studied. Expression of the VEGF receptor Flk-1, but not Flt-1,
was increased in colonic tissue of azoxymethane-treated rats compared with
control rats. The expression of Flk-1 was mainly localized in the epithelial
cells, particularly in the lower part of the crypt. Aspirin treatment reduced
Flk-1 expression in both control and azoxymethane-treated rats. Caspase-3
activity, which has been considered as an apoptotic index, was almost
undetectable in azoxymethane-treated rats. Aspirin treatment stimulated caspase-3
activity. Overexpression of eNOS, VEGF and its receptor Flk-1 occurred early
after azoxymethane administration in rat colonic tissue, even before
morphological changes associated with tumour generation were observed, and
aspirin prevented the overexpression of both eNOS and VEGF receptor Flk-1.

Nihon Ganka Gakkai Zasshi. 1986 Sep;90(9):1159-64.
[The inhibitory effects of topically administrated aspirin solution on the
disruption of blood-aqueous barrier after paracentesis].
[Article in Japanese]
Hiramitsu T, Uemura K, Suwa D.

Klin Monbl Augenheilkd. 1985 Jan;186(1):29-31.
[Collapse of the blood-aqueous humor barrier following laser injury--preventive
pharmacotherapy with prostaglandin inhibitors].
[Article in German]
Schrems W.
Laser-induced collapse of the blood-aqueous barrier and the protective effect of
different prostaglandin inhibitors were investigated in the animal study reported
here. As a parameter of the barrier function, the protein concentration in the
aqueous humor was measured using a micromethod. The anterior chamber of 90 eyes
(45 rabbits) was tapped only once, 100 min after the laser procedure. The results
prove that different prostaglandin inhibitors in a systemic or topical
application form can effectively reduce disturbances of the blood-aqueous barrier
after laser surgery. This is also of clinical relevance with regard to laser
iridotomy or trabeculoplasty in glaucoma.

Res Vet Sci. 1984 Jul;37(1):26-9.
Effect of lysine-acetylsalicylate and phenylbutazone premedication on the protein
content of secondary aqueous humour in the dog.
Regnier A, Bonnefoi M, Lescure F.
Inhibitory effects of the anti-inflammatory agents lysine-acetylsalicylate (LAS)
and phenylbutazone (PBZ) on the breakdown of the blood-aqueous barrier by
paracentesis were studied in canine eyes using protein determination of ocular
fluid. In the untreated eyes the aqueous protein value was raised from 0.29 +/-
0.17 (mean +/- SD) g litre-1 at the initial paracentesis to 14.47 +/- 4.10 g
litre-1 at the second paracentesis. Pretreatment with LAS or PBZ had no
significant effect on the protein concentration of the primary aqueous humour.
However the secondary aqueous protein concentration was only 10.05 +/- 7.00 g
litre-1 with LAS and 5.80 +/- 3.83 g litre-1 with PBZ. With both drugs the
maximum inhibitory effect was observed on the gammaglobulins and albumin. These
results suggest that prostaglandins may be involved in the response of the canine
eye to paracentesis and that premedication with LAS or PBZ may be of value in
reducing postoperative ocular inflammation.

Am J Med. 1983 Jun 14;74(6A):83-90.
Distribution of salicylate in lens and intraocular fluids and its effect on
cataract formation.
Cotlier E, Sharma YR, Niven T, Brescia M.
Retrospective studies on cataract development in patients with rheumatoid
arthritis or osteoarthritis revealed a retardant effect of aspirin on diabetic
and non-diabetic cataracts. The effect of aspirin is dose-dependent. The
correlation coefficient between years delay for various cataracts subcategories
versus aspirin taken (in tablets per day X years of intake) was 0.69. The ocular
pharmacokinetics of 14C acetylsalicylic acid or salicylate were determined after
intravenous or intraperitoneal administration to rabbits. 14C acetylsalicylic
acid penetrates rapidly into rabbit lens and aqueous humor after intravenous
administration. After intraperitoneal administration, salicylate levels in rabbit
plasma, similar to those of humans receiving four to six aspirin tablets (325 mg
each), result in accumulation of salicylate by lens (mean +/- SD) of 405 +/- 72
mumoles/g and 620 +/- 30 mumoles/g at two and four hours, respectively. At those
dosages, salicylate is cleared in 24 hours from rabbit plasma and intraocular
fluids, but retained by lens. Penetration of salicylate into rabbit lens and rat
lens is dose-dependent. The retardant aspirin effect in diabetic cataracts is
linked to inhibition of tissue aldose reductase and lens protein glycosylation.
Deceleration of galactose cataract formation in rats occurs after daily
salicylate intraperitoneal injections of 100 mg/kg a day.

Graefes Arch Clin Exp Ophthalmol. 1983;221(2):61-4.
The effect of prostaglandin inhibitors on the laser-induced disruption of blood
aqueous barrier in the rabbit.
Schrems W, van Dorp HP, Mager S, Krieglstein GK.
In four series, each containing five pigmented rabbits, the therapeutic effects
of different anti-inflammatory agents on the laser-induced disruption of the
blood aqueous barrier was investigated. Utilizing an argon laser, the peripheral
iris of the left eye of each animal was coagulated with a total energy input of
1,000 mJ. The right eyes served as controls. After the coagulation the
intraocular pressure was monitored at intervals of 10 min, and the anterior
chamber was tapped for analysis of the aqueous humour 100 min after treatment. In
a fifth group of five rabbits, aqueous humour was analysed without laser or drug
treatment. The protein concentration and the activity of the lactate
dehydrogenase were analysed in all samples of aqueous humour. A significant
effect on the protection of the blood aqueous barrier could be identified in the
eyes pre-treated with indomethacin (2 mg/kg body weight, injected
intramuscularly), and in those pre-treated with dexamethasone (12.8 mg/kg body
weight, injected intravenously; P less than 0.025%). Pre-treatment with aspirin
(20 mg/kg body weight, injected intravenously) also had a protective response in
the eyes treated by laser. The significance of the results of clinical treatment
is outlined.

Indian J Ophthalmol. 1981 Jul;29(2):97-9.
Effect of antiprostaglandin drugs on human blood--aqueous barrier.
Mathur SK, Satsangi UK, Jain GC.