MaggieMae wrote:I'm confused on this iron thing. My husband just had blood work because he is on Tysabri. The nurse told him his iron levels are low and to eat more read meat. Also, a week or so ago, we noticed that his one leg is swollen. We have an appt with his general doctor this week. The nurse said it could be something vascular. Okay! Help me understand. Should I give him iron pills or not? What is the connection? You all understand this much better than I do.
Has anyone ever thought about seeing a hematologist for their MS?
Sometimes the spleen can produce red blood cells too
Regulation of Expression of Iron Binding Proteins in the Nervous System
The projects in my laboratory are designed to understand the cellular and molecular mechanisms by which cells regulate their iron status. Iron is essential for normal function but at the same time too much iron can be toxic. Therefore cells have an exquisite system for regulating iron levels. When these regulatory mechanims become dysfunctional either through damage, disease or genetic modification cell behavior is abnormal and they sometimes die. Iron imbalance is associated with a prooxidative stress and a proinflammatory environment. Much of our work has focused on mechanisms responsible for regulating iron in the brain. One basic function in which iron is required in the brain is for the production of myelin. We have shown that too little iron during perinatal development will result in hypomyelination. We have also provided evidence that iron can contribute to Multiple Sclerosis (MS). We have established that there is too much iron in the brain in a number of neurological disorders including Alzheimer's (AD) and Parkinson's Diseases (PD). In contrast, there appears to be too little iron in the brain in a disorder known as Restless Legs Syndrome. What is clear from our studies is that optimal brain function requires a tightly regulated iron supply and that the iron must be delivered in a timely manner. To determine the mechanism(s) for brain iron delivery and the regulation of those mechanisms we have focused on a number of mouse and rat mutants as a model of human diseases in which the ability to acquire, moblize or store iron has been disrupted. In the context of these studies we have generated a very promising mouse line in which the gene for the iron storage protein, ferritin, has been deleted. This model is helping to understand the contribution of loss of brain iron homeostatic mechanisms to those changes seen in the brain with AD, PD and MS. In the course of these studies on ferritin, we found that in addition to the cytoplasmic location, ferritin can be found in cell nuclei under some conditions. This observation has led us to basic molecular studies on DNA binding and protection as well as intracellular trafficking of ferritin. The evidence strongly indicates that nuclear ferritin is associated with tumorigenesis. Another avenue under exploration in the context of homeostatic mechanisms is the analysis of gene mutations that lead to disruption of iron status. We have identified mutations in the Hfe gene as a risk factor for Alzheimer's Disease and Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease). The Hfe protein is thought to limit iron uptake by cells and a mutation in this protein may promote inflammation and oxidative stress. We also have a line of research aimed at understanding mechanisms of iron uptake into the brain. This line of research should provide insight into how too much iron can enter the brain in disease states. These studies have led to one particularly novel and important finding of a new receptor in the brain for ferritin. This receptor is expressed only by oligodendrocytes in the brain. We are investigating the possibility that the selective expression of ferritin receptors on oligodendrocytes may have medically important implications for Multiple Sclerosis.
In regard to function of iron in the brain, one area of focus is the regulation of those proteins responsible for iron management in cells. The iron management proteins are regulated by cytoplasmic mRNA binding proteins that are known are iron regulatory proteins. Our project is to determine how the cytoplasmic mRNA binding proteins find their target mRNAs. The outcome of these studies may help us understand how a cell can become iron overloaded but also will contribute significantly to our general knowledge of post-transcriptional gene regulation. One additional approach which is aimed at understanding the function of iron in cells is gene expression profiling. In these studies we have asked the question: "what does it mean to a cell at the molecular level to be iron loaded or iron starved". So far, we have identified a dozen novel genes and a number of genes not previously known to be iron responsive. These data are relevant to cancer and Alzheimer's Disease and Restless Legs Syndrome.
Are venous stenoses the cause or products of MS?
Finally, an additional possibility could be related to the side effects of MS drugs on the venous wall although these have never been reported.
In this study we described the association between MS and the altered modality of venous return determined by extracranial multiple venous strictures. In our controls, venography quite resembled the normal imaging of extracranial cerebrospinal veins. 25 The hampered cerebrospinal venous drainage in patients with MS determines a complex haemodynamic picture defined as CCSVI. It is characterized by multiple substitute circles, with a very high incidence of reflux in both intracranial and extracranial venous segments and loss of the postural regulation of cerebral venous outflow.
The mechanism underlying this reflux differs from the reflux caused by
incompetence of the jugular valve. In the latter case, valvular insufficiency tested with Valsalva can be related to a picture of transient global amnesia.14
In our study the reflux occurred in any body position without the need to elicit it by a forced movement, suggesting that it is not an expression of valvular incompetence but rather of a stenosing lesion that cannot be crossed with postural or respiratory mechanisms, thereby becoming a long-lasting reverse flow.
Substitute circles are alternative pathways or vicarious venous shunts28 (Fig. 3) that allow for the piping of blood toward available venous segments outside the CNS. In accordance with the pattern of obstruction, both the intracranial and the intrarachidian veins can also become substitute circles; they permit redirection of the deviated flow, preventing intracranial hypertension. However, over time they become overloaded because they carry two different flows, their own draining flow and the shunted flow (Fig. 3).
We also observed that the PP course was related to a CCSVI pattern significantly different as compared to RR and SP, suggesting that the location of venous obstruction plays a key role in determining the clinical course. For instance, PP course, characterized by a slowly progressive syndrome with spastic paraparesis and MRI demonstration of MS plaques in the spinal cord, 20,30-32 was significantly associated to obstruction at several levels of the azygous vein and of the lumbar plexuses (type D pattern, Fig. 3, Table III). In
this situation venous blood of the spinal cord can be drained only in an
upward direction, and is shunted toward the venous plexuses inside the spine (Fig. 3, 4), contributing to explain the correlation between type D and spinal cord involvement in PP patients.
Moreover, the absence of Doppler and venographic features of CCSVI in controls suggests that venous obstructions may be causative of MS rather than a coincidental finding.
Interestingly, similar venous stenoses considered to be congenital
malformations have been described in other human diseases, i.e.,
membranous obstruction of the inferior vena cava and a minor group of
chronic venous diseases of the lower limbs.27-28 Such venous obstruction
brings about an insufficient venous drainage, respectively at the level of the liver and of the cutaneous tissue, subsequently causing inflammation,
sclerosis, and degenerative lesions.24-25,36
Finally, on the bases of our study we could propose the introduction of the ECD-TCCS protocol when a patient presents the first acute episode of demyelinating origin, mostly involving the optic nerve, the so-called clinically isolated syndrome (CIS).
Currently, only longitudinal clinical and MRI observation in time and space is capable to establish the possible conversion of a CIS into CDMS.20
Terry wrote:Lol, Cheer. I know my smoking gets your goat.
Zamoboni didn't actually say that there was leakage of the blood into the brain, did he?
I spent the overnight Thursday night with my daughter-in-law at the ER. Probably she has a seroma after a c section. A seroma is caused by leaking blood vessels. They do not leak blood, but a clear fluid. I wonder what is in that fluid. I had no idea that a vessel could leak anything but blood.
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