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50 Side Effects posted for zhejiang university

April 20th
2008
12:36 PM

Singulair does interact with the astrocyte in the brain.

The role of the cysLT1 receptor (Singulair blocks this receptor) and the astrocyte in the brain has been studied. For anyone from Merck to say that there are no mechanisms by which Singulair can affect the
brain is ludicrous. If the Chinese researchers are correct, then Singulair very clearly affects the brain. Certainly, we don't know exactly how or when the effect would be good or bad. Under what circumstances would it be beneficial and under what circumstances would it be harmful.

For quite a while, researchers have been hypothesizing about the role of the astrocyte in brain function. If we go to look for theories, we will find them. Here is the theory of Dr. Dale Antanitus. I am no here to promote anyone's theory in particular but just to point out that they exist.

http://www.antanitus.com/hypothesis

We can see that the Chinese researchers have gone forward to look at potential links between the cysLT1 receptor (Singulair receptor) and inflammatory response in the brain. The 2008 study showed a link between the astrocyte and the cysLT1 receptor (Singulair receptor)

1: Glia. 2008 Jan 1;56(1):27-37. Links
Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation.

Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, People's Republic of China.

We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT(1) and CysLT(2) receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24-72 h after recovery. Inhibition of phospholipase A(2) and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT(1) receptor mRNA and protein, while moderate OGD induced the expression of CysLT(2) receptor mRNA. Exogenously applied leukotriene D(4) (LTD(4)) induced astrocyte proliferation at 1-10 nM and astrocyte death at 100-1,000 nM. The CysLT(1) receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT(2) receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD(4) (100 nM) increased the expression of CysLT(2) receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT(1) receptor-mediated proliferation and CysLT(2) receptor-mediated death. (c) 2007 Wiley-Liss, Inc.

PMID: 17910051

The astrocyte has been studied to see how it functions in the brain. The astrocyte:

1. may perform a role in the physical structuring of the brain
2. may perform a role in providing neurons with nutrients
3. may perform a minor role in the maintenance of the blood brain barrier
4. may perform a role in neurotransmitters
5. may perform a role in the regulation of ion concentration in the extracellular spaces
6. may perform a role in neuronal regulation of blood flood
7. may perform a role in the protection and repair of neurons

TO LIE TO PEOPLE REGARDING THEIR HEALTH IS CRIMINAL AND SHOULD BE PROSECUTED. PEOPLE OUT THERE ARE GETTING SICKER IF THEY ARE EXPERIENCING SIDE EFFECTS BECAUSE MERCK IS LYING. SOME PEOPLE MAY NOT EXPERIENCE SIDE EFFECTS BUT WHY NOT TELL THE TRUTH AND SAY THAT THERE COULD BE SOME PEOPLE WHO HAVE PSYCHIATRIC SIDE EFFECTS BECAUSE THERE IS A PATHWAY FOR THAT TO HAPPEN.

-- By concernedcitizen | Reply | (2) replies | Private Message me

April 2th
2008
5:30 PM

(I posted this before but after receiving some e-mail, I have revised a few sentences to hopefully make it more understable. )

I would like to share this information with everyone. First, I would like to caution all that it does not prove anything regarding the negative side effect of Singulair but it does suggest that there might (only might) be a physiological cause for any side effect that could be attributed to brain function. A Chinese team has been studying the receptor (Cysteinyl leukotrienes receptor 1) that is targeted by Singulair and is responsible for the method of action that makes Singulair successful. Here is one of their studies.

1: Neurosci Lett. 2004 Jun 17;363(3):247-51. Links Expression of cysteinyl leukotriene receptor 1 in human traumatic brain injury and brain tumors.Zhang WP, Hu H, Zhang L, Ding W, Yao HT, Chen KD, Sheng WW, Chen Z, Wei EQ. Department of Pharmacology, School of Medicine, Zhejiang University, 353, Yan An Road, Hangzhou 310031, PR China. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators. CysLT receptor 1 (CysLT(1)) is one of the two CysLT receptors that has been cloned. Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown. The objective of this study was to examine the distribution of CysLT(1) by immunohistochemical analysis in human brains with traumatic injury or tumors. CysLT(1) was expressed intensely in the microvascular endothelial cells in both normal and abnormal conditions. At 8 days after traumatic injury, microvascular regeneration was found and all of the endothelial cells highly expressed CysLT(1). In gray and white matters of the normal regions of the brain, CysLT(1) was expressed weekly or not at all. However, the CysLT(1) expression increased in the neuron- and glial-appearing cells in gray and white matters after traumatic brain injury. CysLT(1) was also detected in astrocytoma, ganglioglioma and metastatic adenocarcinoma, and the expression in the neuron- and glial-appearing cells around brain tumors increased robustly. PMID: 15182953

Here is the relevant part of the study. "Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown." That sentence says that these scientists believe that CysLT1 exists in the brain but they did not know what the location in the brain was. Then they did this study which showed that the receptor existed in the tissues of the brain that are listed above and are too complicated to discuss here.

It is logical to assume that if a receptor exists in any part of the body that it has a function in other words it does something or tells some other part of the body to do something. They have not proved (that takes many studies) what part of the brain or what the receptor does in the brain or what the effect on the body is if the receptor does not do it's job. We do know that Singular (montelukast, Cysteinyl leukotriene receptor 1 antagonist) blocks this particular receptor so if the receptor exists in the brain that it COULD BE POSSIBLE that Singular prevents this receptor in the brain from doing it's job whatever that is. I know that it is difficult to argue with doctors. This drug has been around a long time. It would be difficult to understand why we are just learning about problems after so long a period of time. I can see from all of these responses that these problems are very real. Of course, we have no idea if Singulair is related or not. But if you need something supportive to show that it is not impossible for them to be related even though there is no proof that they are related, you could print this out and discuss it with your doctor.

This isn't proof of anything but at least it might be a clue. It just shows that it is not impossible that Singular affects brain function in some way.

-- By concernedcitizen | Reply | (1) replies | Private Message me

April 2th
2008
2:06 PM

I would like to share this information with everyone. First, I would like to caution all that it does not prove anything regarding the negative side effect of Singulair but it does suggest that there might (only might) be a physiological cause for any side effect that could be attributed to brain function.

A Chinese team has been studying the receptor (Cysteinyl leukotrienes receptor 1) that is targeted by Singulair and is responsible for the method of action that makes Singulair successful. Here is one of their studies.

1: Neurosci Lett. 2004 Jun 17;363(3):247-51. Links
Expression of cysteinyl leukotriene receptor 1 in human traumatic brain injury and brain tumors.Zhang WP, Hu H, Zhang L, Ding W, Yao HT, Chen KD, Sheng WW, Chen Z, Wei EQ.
Department of Pharmacology, School of Medicine, Zhejiang University, 353, Yan An Road, Hangzhou 310031, PR China.

Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators. CysLT receptor 1 (CysLT(1)) is one of the two CysLT receptors that has been cloned. Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown. The objective of this study was to examine the distribution of CysLT(1) by immunohistochemical analysis in human brains with traumatic injury or tumors. CysLT(1) was expressed intensely in the microvascular endothelial cells in both normal and abnormal conditions. At 8 days after traumatic injury, microvascular regeneration was found and all of the endothelial cells highly expressed CysLT(1). In gray and white matters of the normal regions of the brain, CysLT(1) was expressed weekly or not at all. However, the CysLT(1) expression increased in the neuron- and glial-appearing cells in gray and white matters after traumatic brain injury. CysLT(1) was also detected in astrocytoma, ganglioglioma and metastatic adenocarcinoma, and the expression in the neuron- and glial-appearing cells around brain tumors increased robustly.

PMID: 15182953

Here is the relevant part of the study.

"Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown."

That sentence says that these scientists believe that CysLT1 exists in the brain but they don't know what the location in the brain is.

It is logical to assume that if a receptor exists in any part of the body that it has a function in other words it does something or tells some other part of the body to do something. So we don't know what part of the brain or what the receptor does in the brain or what the effect on the body is if the receptor does not do it's job.

We do know that Singular (montelukast, Cysteinyl leukotriene receptor 1 antagonist) blocks this particular receptor so if the receptor exists in the brain that it COULD BE POSSIBLE that Singular prevents this receptor in the brain from doing it's job whatever that is.

I know that it is difficult to argue with doctors. This drug has been around a long time. It would be difficult to understand why we are just learning about problems after so long a period of time. I can see from all of these responses that these problems are very real. Of course, we have no idea if Singulair is related or not. But if you need something supportive to show that it is not impossible for them to be related even though there is no proof that they are related, you could print this out and discuss it with your doctor.

This isn't proof of anything but at least it might be a clue.

-- By concernedcitizen | Reply | (2) replies | Private Message me


 

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