We are only a fraction of our cells.

Apparently the majority of the cells in the human body are not human. In fact if you were to look at all the cells in my body the majority of them would be bacteria. The human microbe is just recently being investigated thanks to advancing technology such as gene sequencing and researchers are discovering some pretty interesting things. For example some bacteria seem to be host specific; every person could have a unique bacterial “fingerprint”. The human microbe is present all over a person’s body. There are populations in the nose, mouth, skin, urogenital tract, and GI tract. Fluxuations in the bacterial communities of the human gastrointestinal tract could be responsible for IBD.

-Randy

Citation:
American Society for Microbiology. "Humans Have Ten Times More Bacteria Than Human Cells: How Do Microbial Communities Affect Human Health?." ScienceDaily 5 June 2008. 10 October 2009 .

Gum Disease and Stroke - Fact or Fiction?

I know this is a little late, but I talked to a dentist about this article because I was wondering how inflammation in the mouth was related to strokes and it is quite surprising how the health of a person's teeth can affect his or her overall health! Periodontal disease is a bacterial infection that can attack the gums and bone that hold teeth in place. The periodontitis that is associated with the disease causes the inflammation. This is the inflammation of the bone tissue. When you have periodontal disease, the decay (bad bacteria that is to say) can infect the gums and form spaces or gaps around the teeth that are called pockets. The decay can be so deep that it builds BELOW the gum line. The only thing that can help in reversing this is your dentist and a procedure known as scaling (removing plaque, tarter, and stains from around the surface of the tooth) and root planing (removing the bacteria from below the gum line and on the roots and promote healing). If left untreated, this bad bacteria can enter the bloodstream because there is blood supply at the bottom of the tooth that meets with bigger vessels. As a consequence, this bacteria can circulate throughout your body. Gross! This bacteria has been found to be the same bacteria responsible for plaques that can cause heart attack and stroke. He also told me as a side note that there were studies done in a hospital setting that people who didn't clean their tongues vs. those who did (you get rid of the bacteria responsible for bad things in the mouth), had a higher risk of pneumonia. It's therefore amazing how important it is to take care of your teeth and gums because it can be linked to problems in the rest of the body.

Sources: A Dental Professional (a DDS in practice for over 20 years) and a pamphlet about periodontal disease ("The most intrusive guests your mouth will ever meet").

Stroke and Aspirin Therapy

I was reading somewhere the other day that aspirin was used for prevention of strokes and wondered if it was used more for it's anti-platelet or anti-inflammatory effects. Aspirin was used at one point for it's anti-inflammatory effects (not for stroke, but more for arthritis), but there was gastric irritation and possible bleeding associated with it. That was also due to it's high dosage in the past (two tablets three times a day). Now, it is taken usually once a day for its anti-platelet effects. Aspirin alters platelet function by suppressing two factors required for platelet aggregation: thromboxane and prostaglandins. By disrupting platelet aggregation, aspirin is able to thin the blood and therefore, reduce the possibility of blockages in the vessels that could lead to an ischemic stroke or even a heart attack. An interesting fact that I discovered was that Plavix functions the same way as aspirin, but it is prescribed because in clinical studies, it was proven to be an even better anti-platelet aggregator than aspirin because it acts on a different receptor.

Sources:
http://www.stroke.org/site/DocServer/NSAFactSheet_SecondaryStrokeRisk_7-09.pdf?docID=7064
Grau, Armin J. et. al. "Platelet Function Under Aspirin, Clopidogrel, and Both After Ischemic Stroke"" Stroke 34.12 (2003): 849-55.

There is some evidences that smoking is harmful for your health and it induces epigenetics effects,but that is interesting in IBD patients if they quit smoking their symptoms get worst.

What does that mean? Smoking reduces inflammation,or how one factor has different effect in our body?

Tumeric is a spice that comes from the root Curcuma longa, a member of the ginger family, Zingaberaceae.
Turmeric has been used for its medicinal properties for various indications and through different routes of administration, including topically, orally, and by inhalation.
Curcumin, a yellow pigment from Curcuma longa, is a major component of turmeric and is commonly used as a spice and food-coloring agent. It is also used as a cosmetic and in some medical preparations. The desirable preventive or putative therapeutic properties of curcumin have also been considered to be associated with its antioxidant and anti-inflammatory properties.
Curcumin was found to have a miraculous power in anti-inflammatory response.
The natural anti-inflammatory activity of curcumin is on a par with steroidal drugs
and nonsteroidal drugs, which have dangerous side effects.
That is really interesting to see any effect of curcumin on IBD,without toxicity?

Canine Stroke Symptoms

I came across this interesting article about stroke symptoms for dogs. I have a dog and am sure many of the people that read this blog might as well. Do you know if your dog is having a stroke? Their symptoms are very different than that of humans and appear very suddenly.
Some symptoms include:

* tilting the head to the side
* walking in a circle
* turning the wrong way when called
* eating out of only one side of the food bowl
* loss of balance
* lethargy/acting tired
* loss of bladder and bowel control
* blindness
* sudden behavioral changes

IF any of these are noticed by the dog owner, take your pet to the vet immediately.
The causes of canine stroke are similar to that of humans ie: high blood pressure, heart disease, and diabetes to name a few.

www.dog-health-guide.org/caninestrokesymptoms.html

Birth Control can lead to stroke

Studies have shown that The NuvaRing Birth Control Ring, Ortho Evra Patch and the birth control pill Yasmin/YAZ have health risks such as blood clots found in the legs and lungs, that can lead to stroke and also heart attack. These certain types of birth control options expose young women to increased levels of estrogen than normal birth control choices. So women who have higher estrogen levels may be more at risk for stroke. The FDA has issued warning letters about these particular birth control options. According to the FDA, the commercials for Yasmin falsely state the efficacy of the pill as well as minimizing the health risks related to taking this pill. Women should not be taking the pill if over the age of 40. Hormone Replacement Therapy is used pre and post menopausally to replenish the estrogen and progesterone hormone levels that are no longer being produced by the body naturally. Taking these replacement hormones also increase the chance of stroke if not taken correctly. Careful dosing and monitoring of estrogen is necessary to protect the brain from stroke.

Lymphocyte Lifetimes?

A large portion of the research in my lab focuses on determining anti-viral drug concentrations in PBMCs. An interesting question has come up recently, and a quick literature search did not yield any of the answers we were looking for...so I figured I'd try asking all of you fine scientists. Does anyone know, or know where to look to find average lifetimes for lymphocytes...specifically cells with CD8 or CD4, as well as B cells and monocytes?
Thanks in advance.

A New Definition

The term brain attack is starting to be used in hospitals in place of the term stroke. Accompanying this new term is also new advances in MR imaging, and neuroprotective drugs. Overall as time goes on it is important to educate the patient so that they can receive immediate medical aid. 

(http://www.ingentaconnect.com/content/rcop/cm/2002/00000002/00000001/art00016)

The use of the term brain attack is to stress the urgency to the patient that immediate care is needed. Also the past term for an acute stroke by definition is that the effects are suppose to last for longer that 24 hours. Therefore brain attack disallows for the delay of action.  

The same protocol of taking aspirin, and intravenously breaking up the thrombis, while being admitted to the stroke unit is still advised for patients on the onset of a brain attack within 3 hours. However in the UK only 33% of patients arrive within 3 hours after suffering a brain attack. 

Pregnancy and the Risk of Stroke

This is a late post from earlier this week, however; I found an article from the New England Journal of Medicine that was a little different from the topic we talked about the last two weeks. (http://content.nejm.org/cgi/content/full/335/11/768)

The risk of stroke for pregnant women are greater in the first six weeks after delivery and not during the actual pregnancy according to this study.

 Authors Kittner and Stern refuted the belief that pregnancy increased the likelihood of cerebral infarctions and intracerebral hemmorages. In fact from an earlier record from the Mayo Clinic from 1955 to 1979 proof was further given when only one woman suffered an ischemic stroke and no record of intracerebral hemmorage or subarachnoid hemorrhages and found that about 4 in 100,00 women suffered a cerebral infarction during deliveries.

The reason for the increase of strokes postpartum vs. during pregnancy can be attributed to the change in hormones during delivery with the addition of lower blood volume. 

 

Stroke signs

During the past two weeks in class we talked about Stroke. Mainly we discussed about the after affects of stoke. I know that people other than our two combined classes look/read this blog and thought that it might be helpful if someone put some information about the signs and symptoms of a person having a stroke so that they could get the care they need within that critical time window.

Strokes occur when parts of the brain dies due to the lack of blood. About 85% of strokes are consider being an ischemic stroke or clogged vessel stroke. This occurs usually by a blood clot or fatty deposits blocking the vessels to that no adequate blood flow is happening to the brain. The other 15% of strokes occur by having a burst vessel or hemorrhagic stroke. This is caused by blood vessels being ruptured that in turns prevent normal blood flow to the brain and allows blood to leak into the brain tissue itself.

Strokes early symptoms are often ignored. Some signs of stroke include:
• Sudden numbness or weakness in the face, arm or leg.
• Sudden confusion, trouble speaking or understanding speech.
• Sudden trouble seeing.
• Sudden trouble walking or dizziness
• Sudden, severe headache with no known cause.

Another way of looking at the symptoms/early sign is using the anagram F.A.S.T.
Facial weakness: most commonly the person is asked to smile. See if the person’s mouth or eyelids have drooped.

Arm weakness: see if the person is able to raise both arms.

Speech problems: can the person repeat a simple sentence or speak clearly?

Test all three symptoms: If the person happens to fails any of the tests, call 911 immediately.

So always remember to act F.A.S.T. it could save a life.
Source:
http://www.crozer.org/CKHS/Hidden/Services/Stroke+Care/Warning+Signs+and+Risk+Factors+of+Stroke.htm
http://www.strokeinfo.org/

Brain Infarction and the Clinical Expression of Alzheimers Disease.

Snowden et al. performed a study of how different lifestyle choices such as getting a college education or maintaining a high level of mental activity throughout life can affect cognitive function as a person ages on a group of nuns in "The Nun Study". They collected data regarding lifestyle choices, monitored the changes in the nuns' cognition function as they aged, and performed autopsies on the nuns' brains after they died.

One of the objectives of "The Nun Study" was to determine the relationship between brain infarction and the clinical expression of Alzheimer disease. To accomplish this objective physical manifestations of brain infarction and Alzheimer disease that were found at autopsy were compared to the results of cognition tests for dementia and Alzheimer's disease performed by the nuns during life. Lacunar and large brain infarcts were used as markers for infarction and senile plaques and neurofibrillary tangles in the neocortex were used markers for Alzheimer's disease. The study found that of those that met the criteria for Alzheimer disease, those that had brain infarcts had lower cognitive function and a higher prevalence of dementia than those that did not exhibit infarcts. Of those that didn't meet the criteria for Alzheimer disease, brain infarcts were only weakly associated with poor cognitive function and dementia. An especially high level of dementia was found in participants that had lacunar infarcts in the basal ganglia, thalamus, or deep white matter of the brain. However, fewer neuropathologic lesions of Alzheimer's disease in these areas appeared to result in dementia in those with lacunar infarcts as compared to those without lacunar infarcts. In all study participants, there was a strong association between atherosclerosis of the circle of Willis and lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may lead to brain infarction that may play an important role in determining the presence and severity of the clinical symptoms of Alzheimer's disease.

Results and more information from "The Nun Study" have been published in "Aging With Grace" by Dr. David Snowden.

Reference:

Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR.
"Brain infarction and the clinical expression of Alzheimer disease. The Nun Study."
JAMA. 1997 Mar 12;277(10):813-7

CD4+ T cells play a role in mammary carcinogenesis

It is becoming more apparent that mammary carcinogenesis may be promoted by the immune system resulting in worse prognosis in late-stage disease patients¹. The role of CD4+ T cells in promoting invasion and metastasis of mammary adenocarcinomas by regulating tumor-associated macrophages (TAMs) has recently been established.¹ CD4+ T_H0 cells are known to differentiate into multiple subtypes, T helper 1 (T_H1), T helper 2 (T_H2), T helper 17 (T_H17), T regulatory (Treg), and T follicular helper (Tfh). T_H2 cells are preferentially expressed in the MMTV-PyMT model of mammary carcinogenesis and have been shown to regulate a specific type of macrophage known as the alternatively activated (M2) macrophage. T_H2 cells have been shown to produce IL-4 attracting M2 macrophages, whereas T_H1 cells are known to be antitumorigenic, secreting IFNγ.¹ M2 macrophages present in a solid tumor, also known as M2 TAMs, are capable of providing an active invasive and metastatic environment during mammary carcinogenesis by expressing epidermal growth factor (EGF). The activation and selection of T_H2 cells during mammary carcinogenesis however, remains unknown.

T_H2 cells have the ability to activate M2 TAMs during mammary carcinogensis and suppress the activation of T_H1 cells, resulting in progression and an increase in metastatic potential.¹ Understanding the preferential activation of T_H2 cells during mammary carcinogenesis may help develop an anticancer therapeutic that would better target the specific activation of the cell population that is promoting a protumor environment, lessening the chances of metastasis and increasing the survival of patients with breast cancer.

1. DeNardo DG, Barreto BJ, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, and Coussens LM. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 2009: 16:91-102.

Leukocyte Accumulation in Venules following Stroke

Dr. Leslie Ritter’s article “Leukocyte Accumulation and Hemodynamic Changes in the Cerebral Microcirculation During Early Reperfusion After Stroke” addresses the fact that leukocytes play a major role in reperfusion injury following an ischemic stroke. The MCAO-R model was used and is an appropriate method because it simulates the majority of human ischemic strokes. This model along with the use of fluorescence microscopy allowed the researchers to observe the patterns of leukocyte accumulation and the hemodynamic changes in the cerebral microcirculation. This study shows how the leukocyte response, which is a component of the inflammatory cascade, is initiated following cerebral ischemia and reperfusion.

The article describes two important results found from the experiments. First of all, the researchers found that 2 hours of middle cerebral artery occlusion (MCAO) followed by 1 hour of reperfusion leads to significant leukocyte rolling and adhesion to cerebral venules. In the arterioles and capillaries, however, leukocyte rolling and adhesion increased only slightly compared to the control group but was not significant. Why do the white blood cells adhere more in the venules compared to other parts of the cerebral microcirculation? I am curious as to why there was a significant increase in leukocyte accumulation in the venules but not in the arterioles and capillaries. The other important result I wanted to mention is that the researchers found the shear rate was significantly reduced in venules following early reperfusion after MCAO. Did the leukocyte accumulation in the venules lead to a decrease in the shear rate? If not, what other factors might have caused this decrease?

Reference: http://stroke.ahajournals.org/cgi/reprint/31/5/1153

Mucosal Tolerance to E-selectin

In the paper "Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury" it is shown that mucosal tolerance to E-selectin can reduce stroke size and the extent of post-ischemic brain injury. However these beneficial effects were seen in the group given a E-selectin booster. One group was given E-selectin every other day for ten days (the single tolerance group) and the second group was given E-selectin on the same schedule but then recieved another dose 11 days later (the booster tolerance group). The fact that a significate decrease in stroke size was only seen in the booster group probably means that the effect of E-selectin tolerance is only short-term. I wonder if E-selectin tolerance can be achieved in the mucosa of the digestive system. If so maybe this treatment can be taken in pill form as a preventative measure for people at risk for stroke. A nasal spray may be possible too.

Stroke and Lifestyle

This is from a review article that looked at the association of
environmental factors, nutrition, alcohol, tobacco, education, ischemic stroke and cerebral hemorrhage:

The link between air pollution and stroke risk has become evident. Low education levels and depression are established as risk factors of stroke. This is also true for heavy alcohol consumption, although moderate drinking may be protective. Active and passive smoking are independent risk factors, and a smoking ban in public places has already reduced cardiovascular events in the short term. Physical activity reduces stroke risk; overweight increases it. However, clinical trials to assess the effect of weight reduction on stroke risk are still lacking. Fruits, vegetables, fish, fibers, low-fat dairy products, potassium and low sodium consumption are known and recommended to reduce cardiovascular risk. Data on omega 3 fatty acid, folic acid and B vitamins are inconsistent, and antioxidants are not recommended.

Interleukin-10 gene polymorphism

The articles from this week discussed the important role of interleukin-10 in post ischemic stroke. We understood that the lack of IL-10 could result in further brain injury from excess inflammation caused by unregulated cytokines secretions, as well as less chance of recovery (no significant reduction of infarction size or progressed physical movements and verbal ability).
One of the articles raised a question about why stroke patients exhibit a different anti-inflammatory profile. It mentioned briefly about the interleukin-10 gene polymorphism and therefore I did some further research on this issue.
Various studies have shown the correlation between IL-10 polymorphism and a higher risk of death or lower ability to deal with infections and diseases.
The particular study I read was in the case of sudden infant death syndrome (SIDS) where the studies found a difference in the percentage of genotypes between the control and experiment groups. The study discovered higher percentage genotype G21/G22 of the SIDS patients than in the controls. The individuals with an unfavorable IL-10 genotype exhibited abnormal IL-10 production which leads to imbalanced immune response upon infection.

My question towards these various studies is - if IL-10 gene polymorphism is known to be the main reason causing lower secretion of IL-10, perhaps many diseases or deaths (including stroke) could be prevented? A few research articles I read that are related to IL-10 gene polymorphism were pulmonary diseases, Hodgkin's Lymphoma, SIDS, etc. However, I have not yet read about any methods or technology to perform on newborns for diagnosing such deficit of genes.

Opdal SH, Opstad A, Vege A, Rognum TO
IL-10 gene polymorphisms are associated with infectious cause of sudden infant death.
Institute of Forensic Medicine, University of Oslo, Rikshospitalet University Hospital, 0027 Oslo, Norway.
Human Immunology. 2003 Dec;64(12):1183-9

Can Magnesium Supplementation Help Reduce Brain Damage and Cytoskeletal Protein Alterations?

Several studies have shown that central nervous system injury results in changes in blood and brain magnesium (Mg) levels. Decreases in intracellular magnesium ion levels resulting from brain injuries can compromise critical cellular functions. In a recent study, researchers looked at how pre brain injury magnesium deficiency and post-injury magnesium treatment affected cell cytoskeletal protein alterations after brain injury. Cytoskeletal protein alterations have been shown to lead to abnormal structural changes and neuronal cell death. They have also been linked to pathological alterations in brain plasticity, which may be a key player in neuronal regeneration or continued degeneration after stroke. The potential for magnesium supplementation to affect brain damage was looked at through calcium sensitive pathways that can activate calpains which can degrade microtubule-associated protein-2 (MAP-2) and spectrin. The degradation of cytoskeletal proteins MAP-2 and spectrin were looked at as markers of neuronal injury.

To test this idea, rats were fed a magnesium deficient diet for two weeks prior to induced brain injury or supplemented with a magnesium chloride solution 10 minutes post injury. It was found that magnesium treatment post injury reduced brain cell loss and reduced the amount MAP-2 and spectrin alterations. The magnesium deficient rats had a greater level of cell death and were observed to have cytoskeletal protein alterations in the cortex and hippocampus not observed in the control or magnesium treated groups. This experimentation revealed both a possible treatment and mechanism behind traumatic brain injury. Magnesium administration in the acute post-traumatic phase of brain injury helps maintain cytoskeletal integrity and reduces cortical cell loss and the cytoskeletal alterations responsible for cell death may be modulated by calpains.

The results of this study show that it may be beneficial to supplement one's diet with magnesium from a source such as a daily multi-vitamin. I am curious toward the idea of magnesium supplementation as means to treat stroke patients. It would be interesting to see if magnesium administration to stroke patients in the acute phase of stroke would lead to a decreased level acute phase and/or long-term cell death.


Reference:
K. Sattman, F. Bareyre, M.S Grady, T. McIntosh. "Acute Cytoskeletal Alterations and Cell Death Induced by Experimental Brain Injury Are Attenuated by Magnesium Treatment and Exacerbated by Magnesium Deficiency." Journal of Neuropathy and Experimental Neuroscience; Vol 60, No. 2. February 2001, pp. 183-194.

immune involvement in schizophrenia and autism

This article discussed here is from a review article, I found the literature reviewed to be quite convincing for a possible link between maternal infection, specifically maternal cytokine response and schizophrenia and autism.

"Over 25 studies have analyzed schizophrenia following influenza epidemics, and the majority have found an increased incidence among exposed offsprings." A variety of other maternal infections, such as maternal rubella, toxoplasm, and genital/reproductive infections and other bacterial infections with schizophrenia. Similarly, research groups such as, "Ciaranello and Ciaranello are concluding that, 'the principal non-genetic cause of autism is prenatal viral infection.' For instance, prenatal exposure to rubella or cytomegalovirus[...]."

The common link between these bacterial and viral infections and offspring developing these disorders "is activation of the maternal immune response." Animal models have been conducted to model maternal bacterial infections, viral infections. One such study with P. gingivalis (involved in periodontal disease) found that P. gingivalis DNA could be found in placentas of affected fetuses and the placentas show elevation of pro-inflammatory and reduction of anti-inflammatory cytokines.

Other studies have mimicked bacterial infection, but modeled maternal immune activation via use of LPS. LPS in these models was administered via IV, intrauterine and IP to pregnant mice, rats, rabbits and ewes. Conclusions from these studies were that the offspring experienced increased anxiety, deficits in social interaction and learning, brain inflammation, and altered microglial immunostaining and PET imaging. Permanent activation of astrocytes and microglial was also detected in adult offsprings.

In both LPS-induced maternal immune activation and P. gingivalis infection, several cytokines were determined to be elevated in the placenta and amniotic fluid. With specific cytokines such at IL-6 remain elevated in the hippocampus of the offspring at 4 and 24 weeks of age. " This is reminiscent of the ongoing state of immune dysregulations in adult autistic and schizophrenic brains," and remember in the LPS model the offspring also had permanent activation of astrocytes and microglial. More impressive in the link of the immune response and specifically IL-6 expression and schizophrenia and autism is that "early over expression of IL-6 in astrocytes causes major neuropathology and decreases seizure threshold and seizures are a common symptom of autism. IL-6 and related cytokines strongly influence many features of brain development and neural repair."

Autistic and schizophrenic adults have permanent elevations of cytokines in the brain, due to this research and the knowledge that injection of cytokines into adults can induce psychiatric symptoms. This further strengthens the link between cytokine induction in the placenta and the development of these disorders. In this review, the authors also point out that there has been reports that some adults and children spontaneous develope autistic symptoms following CNS infection. Under the immune system and cytokine link, this observation begins to make sense since CNS infections are known to induce pro-inflammatory cytokine responses. This adds further evidence that these two disorders may be linked to maternal infection and cytokine generation which may act on the placenta.

I found this compilation of work interesting because it offers potential drug targets, but it also suggests that it may be possible to separate schizophrenia and autism cases, which may lead to a better understanding of what are the risk factors that are attributed to autism development.

Patterson, Paul H. "Immune involvement in schizophrenia and autism: Etiology, pathology and animal models." Behavioral Brain Research 204 (2009) 313-321.