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YaBB - Yet another Bulletin Board
  MS-ihmisten kannattaa huolehtia D-vitamiinin saannista
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1  Tutkimus / Tutkimus / Re: MS ja aivojen imusuonet
 Pvm: Eilen - 00:27:39 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Brain's lymphatic vessels as new avenue to treat multiple sclerosis

https://www.sciencedaily.com/releases/2018/09/180917135939.htm

September 17, 2018
Lymphatic vessels that clean the brain of harmful material play a crucial role in the development and progression of multiple sclerosis, new research from the University of Virginia School of Medicine suggests. The vessels appear to carry previously unknown messages from the brain to the immune system that ultimately trigger the disease symptoms. Blocking those messages may offer doctors a new way to treat a potentially devastating condition that affects more than 2 million people.

The discovery comes from the lab of UVA researchers who identified the lymphatic vessels surrounding the brain, vessels that textbooks long insisted did not exist. In an exciting follow-up, the researchers have determined that the vessels play an important role in not only multiple sclerosis but, most likely, many other neuroinflammatory diseases and in dangerous brain infections.

"Our data suggests that there is a signal coming from the brain to the lymph nodes that tells immune cells to get back into the brain, causing the [multiple sclerosis] pathology," said researcher Antoine Louveau, PhD, of UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG). "This is an important proof of principle that exploring the role of these vessels in different neurological disorders, including multiple sclerosis, is worth it."

Stopping Multiple Sclerosis

The researchers at UVA, led by Jonathan Kipnis, PhD, were able to impede the development of multiple sclerosis in mice by targeting the lymphatic vessels surrounding the brain. They used multiple strategies to block the lymphatics or destroy them with a precision laser. All led to the same outcome: a decrease in the number of destructive immune cells capable of causing paralysis.

"The idea was to prevent more widespread damage to the nervous system," said researcher Jasmin Herz. "If communication of brain inflammation through lymphatic vessels is the root cause of multiple sclerosis, therapies targeting these vessels could be clinically important."

The message from the brain that appears to drive multiple sclerosis remains poorly understood. The researchers can tell the message is being sent, and they can tell what it is instructing the immune system to do, but they don't yet know what mechanism the brain is using to send it. "I think the next step in this specific research is to identify what that signal is. Is it a cellular signal, is it a molecular signal?" Louveau said. "And then to try to target that signal specifically."

The researchers noted that removing the vessels did not stop multiple sclerosis entirely. That suggests there are likely other factors at play -- and much more for scientists to explore.

An Important Proof of Principle

UVA's new research offers important insight into the function and role of the lymphatic vessels that connect the brain to the immune system. In most aspects, they work exactly as scientists would expect -- just like other lymphatic vessels in the body.

"Meningeal lymphatic vessels are quite small compared to other lymphatics in the body, and we and others wondered if this might limit the amount and size of cargo they can pass through," Herz said. "During inflammation, they did not change in size or complexity much, but what was really exciting to discover [was that] they allowed whole immune cells to traffic through them, and we found the molecular cues for that."

But the lab's recent research also highlights the complexity doctors face when trying to manipulate the vessels to benefit human health. For example, blocking the vessels had a benefit in the multiple sclerosis model, but the lab has also shown that the vessels' healthy function is vital to staving off Alzheimer's disease and preventing the cognitive decline that comes with age.

That means that it's unlikely that stopping MS could be as simple as blocking the flow inside the vessels. It also suggests that there is probably no one treatment approach that will work for every neurological disorder. But the emerging importance of the vessels offers doctors an exciting new avenue for tackling neurological diseases.

"These findings on the role of brain-draining lymphatic vessels in MS, together with our recent work on their role in Alzheimer's disease, demonstrate that the brain and the immune system are closely interacting. When these interactions go out of control, pathologies emerge," said Kipnis, chairman of UVA's Department of Neuroscience and director of the BIG Center. "The idea that we could target major neurological disorders through therapeutic manipulation of peripheral structures, such as lymphatic vessels, is beyond exciting. Through our collaboration with PureTech Health, we hope to bring these laboratory findings to improve patients' lives one day."
Kipnis recently signed a deal with biopharmaceutical company PureTech Health to explore the potential clinical applications of his discoveries.




2  Yleinen / MS-jutut / Re: Puutumiset + muut oireet
 Pvm: 16.09.2018 - 05:25:49 
Keskustelun aloitti Susku75. | Kirjoittaja merikihu  
Oikeassa olet, että oireet voivat olla hyvin erilaisia ja ne voivat myös kestää eri aikoja. Usein oireiden kestoa voi lyhentää kortisonitiputuksella (kortisonipulssi). Toivottavasti magneettikuvauksessa löytyy jotain selitystä oireillesi.

3  Yleinen / MS-jutut / Puutumiset + muut oireet
 Pvm: 15.09.2018 - 22:41:52 
Keskustelun aloitti Susku75. | Kirjoittaja Susku75.  
Haluaisin kuulla minkälaisia oireita teillä diagnoosin saaneilla on. Oon ymmärtänyt, että oireet voi olla hyvin erilaisia. Puutumisesta kiinnostaa jääkö puutuminen vaivaamaan aina pidemmäksi aikaa, vai voiko helpottaa suht nopeastikin?

Mulla ei siis ole diagnoosia, mutta silmäongelmien takia mahdollisesti magneettikuvaus on edessä MS-taudin poissulkemiseksi. Mulla nousi silmänpaineet alkuvuodesta huimiin lukemiin. Kontrollien yhteydessä silmistä on löytynyt myös iriitti/uveiitti/iridosyliitti (lääkärit eivät osaa päättää mikä se on ollut..), josta on ollut vaikea päästä eroon. Muita oireita on ollut vuosia (esim sormien puutumista, selkäkipua jne), eikä niihin ole löytynyt syytä. Kuulisin siis mielelläni mitä kaikkia oireita tähän sairauteen voi liittyä.

4  Yleinen / Niksit / kokoonmenevä sähkömopo
 Pvm: 10.09.2018 - 13:38:27 
Keskustelun aloitti sofiia | Kirjoittaja sofiia  
Onkohan kellään kiinnostusta itsestään kokoonmenevään Di Blasi-sähkömopoon? Uudessa Avain-lehdessä on mainos sivulla 21.
Kauppaamassani on erikoisvarusteena kiinteät käsinojat jja väriltään se on tummanharmaa. Mopoa on käytetty kaksi kertaa; tilattiin edesmenneelle isälleni, koska hän toivoi. Ei kuitenkaan pystynyt sitä käyttämään.
Maksettiin siitä 3400e käsinojineen, nyt myyn sen 2800e.

5  Hoito / Oireiden hallinta / Re: Voimattomuus
 Pvm: 09.09.2018 - 17:33:40 
Keskustelun aloitti Tulip | Kirjoittaja hopefully  
Mulla myös voimattomuutta jaloissa. Täytyy varmaan huomenna soittaa neuron polille. Pääsen kyllä kävelemään mutta en uskalla edes lähikauppaan mennä, eilen kävin ja hyvä kun pääsin takaisin kotiin:(

6  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 08.09.2018 - 01:37:21 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
STAT3 can be a therapeutic target for chronic active EBV infection, a fatal disorder

https://www.sciencedaily.com/releases/2018/08/180820113117.htm

August 20, 2018
Tokyo Medical and Dental University(TMDU) study shows that ruxolitinib-induced inhibition of STAT3 activity blocks survival and reduces pro-inflammatory cytokine production in Epstein-Barr virus (EBV)-infected clonally proliferating T- or NK-cells in Chronic active Epstein-Barr virus infection.

Tokyo, Japan -- Chronic active Epstein-Barr virus infection (CAEBV) is an EBV-positive T- or NK-cell neoplasm accompanied by sustained systemic inflammation. Many studies have attempted to understand the case of CAEBV; none have provided a clear explanation, until now.

A research team, led by experts from Tokyo Medical and Dental University(TMDU), investigated the activity of STAT3, a factor that helps to control cell proliferation and survival, in EBV-infected T- or NK-cells in CAEBV. They found that STAT3 was constitutively activated in those cells, reported in Oncotarget, "STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target."

CAEBV is a disorder which has 2 aspects: an inflammatory disorder and a lymphoid neoplasm. During the course, it may progress to chemotherapy-resistant lymphoma or leukemia, or to a life-threatening disorder known as hemophagocytic lymphohistiocytosis. Despite a variety of efforts to control or cure CAEBV, the sole effective treatment has been stem cell transplantation from a HLA-matched donor. Unfortunately, some patients cannot be candidates for this therapy, and there are many side effects.

"Constitutively activated STAT3 has been observed in a variety of primary tumor cells, including other tumors associated with Epstein-Barr virus infection," says Ayoko Arai, corresponding author on the study. "We suspected that STAT3 may be similarly activated in cells from patients with CAEBV."

In the study, increased phosphorylation, an important modification of cellular proteins, was observed on STAT3 in EBV-infected T- or NK-cells from patients with CAEBV. In those same cells from health individuals, the phosphorylation was absent, suggesting that it may provide a useful drug target.

"Our analyses revealed no mutations in STAT3, so we tested whether inhibitors of STAT3 phosphorylation might modify its activity in laboratory-grown," says Erika Onozawa, lead author on the study. "We found that ruxolitinib, a drug that is currently used for treatment of myelofibrosis and polycythemia vera, could suppress the survival of the EBV-infected cells in a dose-dependent manner."

In addition to the ability of ruxolitinib to induce the death of virus-infected T- or NK-cells from patients with CAEBV, the researchers showed that it could block the production of several important inflammatory cytokines that play a role in the progression of CAEBV.

CAEBV is a neoplastic and inflammatory disease that can become extremely destructive for some patients. This study showed that STAT3 could be an important new target for treatment of this disorder, and that ruxolitinib may provide a readily available therapy that may be effectively used in clinical treatment.

7  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 08.09.2018 - 01:31:46 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Scientists find a new way to attack herpesviruses

https://www.sciencedaily.com/releases/2018/08/180828121414.htm

August 28, 2018
Human cytomegalovirus is a leading cause of birth defects and transplant failures. As it's evolved over time, this virus from the herpes family has found a way to bypass the body's defense mechanisms that usually guards against viral infections. Until now, scientists couldn't understand how it manages to do so.

A team of scientists led by Leor S. Weinberger, PhD, the William and Ute Bowes Distinguished Professor and director of the Gladstone-UCSF Center for Cell Circuitry, uncovered the mechanism that allows the virus to replicate. Their study, published in the scientific journal PNAS, could open new therapeutic avenues to treat not only cytomegalovirus, but other viruses as well.

Normally, when a virus enters your cell, that cell blocks the virus's DNA and prevents it from performing any actions. The virus must overcome this barrier to effectively multiply.

To get around this obstacle, cytomegalovirus doesn't simply inject its own DNA into a human cell. Instead, it carries its viral DNA into the cell along with proteins called PP71. After entering the cell, it releases these PP71 proteins, which enables the viral DNA to replicate and the infection to spread.

"The way the virus operates is pretty cool, but it also presents a problem we couldn't solve," said Noam Vardi, PhD, postdoctoral scholar in Weinberger's laboratory and first author of the new study. "The PP71 proteins are needed for the virus to replicate. But they actually die after a few hours, while it takes days to create new virus. So how can the virus successfully multiply even after these proteins are gone?"

The researchers found that, while PP71 is still present in the cell, it activates another protein known as IE1. This happens within the first few hours of the virus entering the cell, allowing the IE1 protein to take over after PP71 dies and continue creating new virus.

To confirm their findings, the team created a synthetic version of the virus that allowed them to adjust the levels of the IE1 proteins using small molecules. With this technique, they could let the virus infect the cell while controlling how quickly the IE1 protein would break down in the cell.

"We noticed that when the IE1 protein degrades slowly, as it normally does, the virus can replicate very efficiently," said Vardi. "But if the protein breaks down faster, the virus can't multiply as well. So, we confirmed that the virus needs the IE1 protein to successfully replicate."

This study could have broad implications for the scientific community, which has been struggling to determine how cells maintain their identity over time. During development, for instance, stem cells choose a path based on the proteins that surround them. But even after these initial proteins disappear, the specialized cells don't change. So, stem cells that turn into neurons during development continue to be neurons long after those proteins are gone.

"The issue is similar for the virus," explained Weinberger, who is also a professor of pharmaceutical chemistry at UC San Francisco. "It was not clear what mechanisms allowed the virus to continue replicating long after the initial signal from the PP71 had decayed to a whisper. Our findings uncover a circuit encoded by the virus that controls its fate and indicate that such circuits may be quite common in viruses."

The new study could lead to a new therapeutic target to attack cytomegalovirus and other herpesviruses, such as Epstein-Barr virus that causes mononucleosis and herpes simplex virus 1 and 2 that produce most cold sores and genital herpes.

8  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 08.09.2018 - 01:24:13 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Increasing Evidence Points to Inflammation as Source of Nervous System Manifestations of Lyme Disease

https://www.elsevier.com/about/press-releases/research-and-journals/increasing-e...

Philadelphia, PA, April 16, 2015
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Lyme disease in humans results from the bite of a tick infected with the spirochete Borrelia burgdorferi (Bb). As Bb disseminates throughout the body, it can cause arthritis, carditis, and neurologic deficits. When the nervous system is involved, it is called Lyme neuroborreliosis (LNB). Clinical symptoms of LNB of the peripheral nervous system may include facial nerve palsy, neurogenic pain radiating along the back into the legs and feet, limb pain, sensory loss, or muscle weakness. Central nervous system involvement can manifest as headache, fatigue, memory loss, learning disability, depression, meningitis, and encephalopathy.
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Some patients with Lyme disease also show evidence of demyelinating neuropathy and slowing nerve conduction. Nerve conduction studies in motor and sensory nerves of the macaques showed that the Bb infection resulted in specific electrophysiological abnormalities (increased F wave latencies and chronodispersion) that could be prevented with dexamethasone.
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“Importantly, we found necrotizing myelitis and degeneration in the spinal cord, neurodegeneration in the dorsal root ganglia, and demyelination in the nerve roots only when lymphocytic inflammatory lesions were also observed in both the central nervous system and peripheral nervous system,” stated Dr. Philipp. “Our results suggest that ongoing cytokine activation in the nervous system can contribute to the persistent symptoms of fatigue, pain, and cognitive dysfunction that patients sometimes experience despite having been treated for Lyme disease.”

9  Tutkimus / Tutkimus / It's the B-cells
 Pvm: 08.09.2018 - 01:15:37 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
B cells among factors leading to brain lesions in multiple sclerosis

https://www.sciencedaily.com/releases/2018/09/180904114644.htm

September 4, 2018

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The body's own immune cells attack and damage the layer that surrounds nerve cells in the brain and spinal cord, which affects their ability to communicate with each other. The disease, which affects around 2.5 million people worldwide, is a common cause of disability in young adults and affects women particularly often. MS can lead to severe neurological disabilities such as sensory problems, pain and signs of paralysis.

B cells activate T cells

A team led by neurologist Roland Martin and immunologist Mireia Sospedra at the University of Zurich (UZH), the University Hospital Zurich (USZ) and researchers at the Karolinska Institute in Sweden has now discovered a key aspect in the pathogenesis of MS. "We were able to show for the first time that certain B cells -- the cells of the immune system that produce antibodies -- activate the specific T cells that cause inflammation in the brain and nerve cell lesions," says Roland Martin, Director of the Clinical Research Priority Program Multiple Sclerosis at UZH.

Novel MS drugs attack B cells

Until recently, MS research had mainly focused on T cells, or T helper cells. They are the immune system's "guardians," which for example sound the alarm if the organism is infected with a virus or bacteria. In about one in a 1,000 people, the cells' ability to distinguish between the body's own and foreign structures becomes disturbed. The effect of this is that the misguided T cells start to attack the body's own nerve tissue -- the onset of MS. However, the T cells aren't the sole cause of this. "A class of MS drugs called Rituximab and Ocrelizumab led us to believe that B cells also played an important part in the pathogenesis of the disease," explains Roland Martin. These drugs eliminate B cells, which very effectively inhibits inflammation of the brain and flare-ups in patients.

B cells' "complicity" revealed

The researchers established the role of B cells by using an experimental in-vitro system that allowed blood samples to be analyzed. The blood of people with MS revealed increased levels of activation and cellular division among those T cells attacking the body's myelin sheaths that surround nerve cells. This was caused by B cells interacting with the T cells. When the B cells were eliminated, the researchers found that it very effectively inhibited the proliferation of T cells. "This means that we can now explain the previously unclear mechanism of these MS drugs," says Roland Martin.

Activated T cells migrate to the brain

Moreover, the team also discovered that the activated T cells in the blood notably included those that also occur in the brain in MS patients during flare-ups of the disease. It is suspected that they cause the inflammation. Further studies showed that these T cells recognize the structures of a protein that is produced by the B cells as well as nerve cells in the brain. After being activated in the peripheral blood, the T cells migrate to the brain, where they destroy nerve tissue. "Our findings not only explain how new MS drugs take effect, but also pave the way for novel approaches in basic research and therapy for MS," concludes Roland Martin.

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Ts. jos käytät lääkkeitä, jotka tuhoavat ainoastaan T-soluja, niistä ei ole apua..

10  Hoito / Lääkitys / Re: Tecfidera
 Pvm: 01.09.2018 - 21:24:14 
Keskustelun aloitti Gwbh | Kirjoittaja Red Kite  
vanilla kirjoitti on 29.07.2018 - 23:44:51:
Eniten huolettaa se JC-positiivisuus, mutta todennäköisesti se on monella meistä käyttäjistä? Verikokeita on näköjään harvemmin kuin Aupagiossa.


Aika todennäköisesti, onhan se 50 - 70 %:lla (lähteestä riippuen) ihmiskunnasta. Lähinnä se muodostuu ongelmaksi sitten, kun leukkarit laskevat alarajan alle ja pysyvät alhaalla. Itsellä on kesän aikana ollut kaikenmaailman ihmepöpöä, joten ensiviikon kontrolli on ihan tervetullut.