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-   -   Internal **** Sphincter Muscle? (https://www.neurotalk.org/multiple-sclerosis/153006-internal-sphincter-muscle.html)

Yorkieville 07-03-2011 05:59 PM

Internal **** Sphincter Muscle?
 
Has anyone with MS been diagnosed with the nerves in this muscle not sending the messages to their brain?

TIA
Chelle

Erin524 07-03-2011 07:30 PM

which muscle is that? I'm assuming the word you used in the thread title was one that's not the usual medical term for whatever muscle it is.

Blessings2You 07-03-2011 07:48 PM

Sphincter ani internus - or a-n-a-l sphincter muscle.

Yorkieville 07-03-2011 07:49 PM

Quote:

Originally Posted by Erin524 (Post 783559)
which muscle is that? I'm assuming the word you used in the thread title was one that's not the usual medical term for whatever muscle it is.

We have two **** sphincter muscles. One, the internal, is involuntary, meaning that we cannot control it, it is controlled by the brain.

The external, we control, consciously, such as when we tighten it, to hold back expelling as, in public, etc.

My internal muscle is not sending the message to my brain, to relax, and allow a bowel movement, etc.

Those are the medical terms as far as I know.

Chelle

Yorkieville 07-03-2011 07:51 PM

Quote:

Originally Posted by Blessings2You (Post 783563)
Sphincter ani internus - or a-n-a-l sphincter muscle.

Thank you Blessings2You, for your clarification.

Chelle

Erin524 07-03-2011 08:04 PM

interesting what the forum's word censor censors. (medical forum, you'd think you'd be able to type that word without getting it starred out)

jackD 07-03-2011 08:13 PM

vinpocetine???
 
You might want to check out vinpocetine.

Besides curing MS and making you much smarter it also helps control smooth muscles.

It helps with some bladder and sphincter muscle control.

Braindead

p.s. I take 10 mg three times a day and look how smart it has made me! Suggest you check PubMed and do a Google search.

Yorkieville 07-03-2011 08:16 PM

Quote:

Originally Posted by Erin524 (Post 783568)
interesting what the forum's word censor censors. (medical forum, you'd think you'd be able to type that word without getting it starred out)

Yes, Erin, I was surprised that it was censored.

Chelle

Yorkieville 07-03-2011 08:18 PM

Quote:

Originally Posted by jackD (Post 783569)
You might want to check out vinpocetine.

Besides curing MS and making you much smarter it also helps control smooth muscles.

It helps with some bladder and sphincter muscle control.

Braindead

p.s. I take 10 mg three times a day and look how smart it has made me! Suggest you check PubMed and do a Google search.

Hi, jackD.

Thank you. I will definitley check out vinpocetine.

I see that it has indeed, made you quite intelligent. :)

Chemar 07-03-2011 08:29 PM

just an FYI that it is vBulletin that has the built in word filters...and not all forums that run on vBulletin are health/medical

so this is *not* us censoring, it is a programming default

Yorkieville 07-03-2011 08:31 PM

Quote:

Originally Posted by Chemar (Post 783576)
just an FYI that it is vBulletin that has the built in word filters...and not all forums that run on vBulletin are health/medical

so this is *not* us censoring, it is a programming default

Thank you, Chemar, for the explanation.

Thought I might have broken a rule on my 1st day here.

Chelle

SallyC 07-03-2011 08:49 PM

Quote:

Originally Posted by Chemar (Post 783576)
just an FYI that it is vBulletin that has the built in word filters...and not all forums that run on vBulletin are health/medical

so this is *not* us censoring, it is a programming default

Well, tell them they're full of ####!!!:D

Yorkieville 07-03-2011 08:52 PM

Quote:

Originally Posted by SallyC (Post 783587)
Well, tell them they're full of ####!!!:D

:D

Chelle

SallyC 07-03-2011 08:54 PM

Yes I have that problem, no I don't have that problem....I'm either constipated or NOT!:rolleyes:

Hope you feel better soon..:hug:

Yorkieville 07-03-2011 08:58 PM

Quote:

Originally Posted by SallyC (Post 783589)
Yes I have that problem, no I don't have that problem....I'm either constipated or NOT!:rolleyes:

Hope you feel better soon..:hug:

It's a miserable problem, and for me, it's gotten to the point, that if stool is too soft, it will not force the internal **** muscle to open. And when it is forced to open, I suffer with rectal pain for hours.

Are we having fun yet?

Thanks, if this Spine Specialist is as good as his reputation, maybe, I'll at least get a DX.

Hug,
Chelle

ewizabeth 07-03-2011 09:10 PM

I really like that I can type **** and it will be bleeped. Yes my **** sometimes gives me problems. My **** sometimes does not cooperate. It is common for MS patients to have problems with their ****.

ewizabeth 07-03-2011 09:11 PM

Sorry Chelle,

I couldn't help myself. :o Anyway, I need to eat a lot of fruit and veggies to make my **** cooperate.

Yorkieville 07-03-2011 09:13 PM

Quote:

Originally Posted by ewizabeth (Post 783598)
I really like that I can type **** and it will be bleeped. Yes my **** sometimes gives me problems. My **** sometimes does not cooperate. It is common for MS patients to have problems with their ****.


:D:D:D:D:D:D

Thanks for the great laugh!

But, I'm sorry you also suffer with your ****.

Chelle

Yorkieville 07-03-2011 09:15 PM

Quote:

Originally Posted by ewizabeth (Post 783599)
Sorry Chelle,

I couldn't help myself. :o Anyway, I need to eat a lot of fruit and veggies to make my **** cooperate.

I loved it ewizabeth!!! :D

Even when I eat lots of fruits & veggies, my **** does not always cooperate.

Chelle

missj 07-04-2011 12:53 AM

yes. dx'ed with a 'paradoxical pubo-rectalis' quite unfortunate.

Yorkieville 07-04-2011 01:29 AM

Quote:

Originally Posted by missj (Post 783637)
yes. dx'ed with a 'paradoxical pubo-rectalis' quite unfortunate.

But, your doctor doesn't know the cause, right?

My G.I. Doc said mine is neurological.

Well, I had better try to get some sleep. We are leaving this afternoon, and I have to at least have my clothes, etc. ready.

Talk to you Thursday evening.

:hug:
Chelle

kicker 07-04-2011 06:30 AM

I was struggling, suffering, took forever - once a week or so got a large constipated into rocks, hurtful poop out. Such an effort and fear of never completing task! Fiber, etc. never seem to help. A urologist told me some Miramax in my coffee every day. Increased some a little every day and found perfect dose. Too much I get squiggles and fudgies. Now 1-2 times a week a formed, but soft enough to easily some out nice size stool is formed and passed. I hate using a drug (Miralax) everyday but the benefits outweigh anything else. Ran it past my GCP and she's fine with it. I'm much happier now!

Yorkieville 07-04-2011 06:48 AM

Quote:

Originally Posted by kicker (Post 783661)
I was struggling, suffering, took forever - once a week or so got a large constipated into rocks, hurtful poop out. Such an effort and fear of never completing task! Fiber, etc. never seem to help. A urologist told me some Miramax in my coffee every day. Increased some a little every day and found perfect dose. Too much I get squiggles and fudgies. Now 1-2 times a week a formed, but soft enough to easily some out nice size stool is formed and passed. I hate using a drug (Miralax) everyday but the benefits outweigh anything else. Ran it past my GCP and she's fine with it. I'm much happier now!

Hi, Kicker.

My problem is that the internal **** sphincter muscle does not send messages to my brain, so, the only way stool passes is when the bowel is too full, and the stool has to be firm enough to force the muscle to open, but, here's the major problem, it will only allow a small amount of stool to pass, and then it clamps tight again. I am unable to empty completely. Soft stool will not pass, at all, and I am miserable, as it makes the nerves in my spine hurt, all the more. My G.I. Doc and I have tried Miralax, etc. but it doesn't solve the issue with the sensory nerves in that muscle.

Hoping my new Spine Specialist will be able to give me some answers on Friday, or at the very least, refer me to someone who can help me.

I'm not Dx'd yet.

Thanks for replying. I really appreciate it.

Now, I have to get ready to go out of town for 3 days.

Chelle

Dejibo 07-04-2011 07:34 AM

I had the same problem in that I would go every if not every other day but it was cement hard chunks and they were painful and sometimes sharp to pass. my gut was sooooo slow! Ended up in the hosptial and dx with gastroparesis (frozen stomach) stuff just sits there, and even if/when it hits the intestine it eeks along at its own slow pace. Frequently the chamber would stay full for a day or more because I dont have the nerve signal that says to let it go.

I stared on a drug called Motillium that we had to order from outside of the USA. My GI was instrumental in helping me figure the whole thing out. My vagus and phrenic nerve have been affected by MS, and therefore stool sits for a loooong time in my intestine till something triggers the opening at the bottm to behave and the opening at the top to push to send more down.

I tried miralax and it worked great for a bit and then....fudgies! couldnt regulate it for my needs. Tried Reglan (which empties your tummy/intestine but it gave me twitches, tics and tremors. Those can turn permenant so I had to stop. Laxatives just made it soft, but not easier to give my brain the signal that it was time.

I had a complete work up by the GI team so they could figure out whch nerves were involved before I went on Motilium. it wont heal the nerves, but it will supply the same signal to the brain that its been missing. I take it 15 mins before each meal I eat and as it starts working, the stomach and intestines get the message that its time to work. I do not have diarrhea, or constipation anymore, just a normal routine most of the time.

Yorkieville 07-04-2011 07:40 AM

Quote:

Originally Posted by Dejibo (Post 783671)
I had the same problem in that I would go every if not every other day but it was cement hard chunks and they were painful and sometimes sharp to pass. my gut was sooooo slow! Ended up in the hosptial and dx with gastroparesis (frozen stomach) stuff just sits there, and even if/when it hits the intestine it eeks along at its own slow pace. Frequently the chamber would stay full for a day or more because I dont have the nerve signal that says to let it go.

I stared on a drug called Motillium that we had to order from outside of the USA. My GI was instrumental in helping me figure the whole thing out. My vagus and phrenic nerve have been affected by MS, and therefore stool sits for a loooong time in my intestine till something triggers the opening at the bottm to behave and the opening at the top to push to send more down.

I tried miralax and it worked great for a bit and then....fudgies! couldnt regulate it for my needs. Tried Reglan (which empties your tummy/intestine but it gave me twitches, tics and tremors. Those can turn permenant so I had to stop. Laxatives just made it soft, but not easier to give my brain the signal that it was time.

I had a complete work up by the GI team so they could figure out whch nerves were involved before I went on Motilium. it wont heal the nerves, but it will supply the same signal to the brain that its been missing. I take it 15 mins before each meal I eat and as it starts working, the stomach and intestines get the message that its time to work. I do not have diarrhea, or constipation anymore, just a normal routine most of the time.

Dejibo,

This is the most useful information I have received. I will talk with my G.I. Doc about the possibilty of ordering Motillium.

You've described my problem to a T!

Thank you so much.

Chelle

Dejibo 07-04-2011 07:55 AM

Took me YEARS to get the GI team to understand that while this doesnt look like an issue, it can be very disruptive to a life. Once the chamber would get full, it just sat and got harder and harder till finally enough material would force it along, and it was so dried and hard by then it was painful. I started to use Prep H on my finger and I would go rescue some of it that I could reach to provide some relief. Then that became a routine because it would provide some relief at the back door for me. You can use KY jelly, or lube or other stuff to really wet your finger to go on your mission, but my choice was prep H. My lower region just wasnt getting the signal that it was time to push it on out. I felt my belly was ready and I felt my lower was ready, but even pushing I felt like I wasnt co ordinated and couldnt get the result I needed, because I was just making my face red, and not getting enough pressure into my bottom to make anything go.

My GI MD at Dartmouth Hosptial in Lebanon NH is making a documented case of me to put in the annual of reports so that others seeking the same type of help can see that other MS patients do have destruction of nerve tissue in the intestine. The lining of our intestine is almost identical to our brain, so if MS attacks the mylin or fat around the brain and eats into the nerve fibers, why cant it eat into the fat around our intestine and eat into the nerve fibers? Most wont put it together because the GI tract has its own nervous system and generally isnt well controlled by the brain, but if you consider that its been attacked the same as the brain would be...you get the answer.

Most folks take Reglan, and its normally well tolerated. Some of us get tics, twitches and grimaces from the drug and it can be permenant nerve damage, so I was tried on a whole host of meds till we had to order from over seas to get Motillium. it does the same thing as reglan, but somehow doesnt make me twitch.

Research gastroparesis. they have several forums out there with tips and tricks on how to eat better, and interventions to help. 50% of the population just takes the reglan and get on with their lives. Some folks have episodes where for 3 months its awful! and then all of a suden things get better for no reason. its like having a flair of MS only in your tummy, not in your head. Some folks have permenant damage from the attacks and have to stay on meds. I have now backed off to once a day with my meds, but wouldnt hesitate to go back up if needed.

Tremendous relief to know I wasnt weird, strange or alone. The MS team took a little longer to come on board till the GI team presented them with study after study or MS presenting in the GI tract. So, we are the pioneers in getting the MS teams to see that this stuff can nick the tummy too. You may meet with resistance, but the more folks that get documented, the more hope those behind us have.

Goodluck write me privately if you wish.

Yorkieville 07-04-2011 08:41 AM

Quote:

Originally Posted by Dejibo (Post 783675)
Took me YEARS to get the GI team to understand that while this doesnt look like an issue, it can be very disruptive to a life. Once the chamber would get full, it just sat and got harder and harder till finally enough material would force it along, and it was so dried and hard by then it was painful. I started to use Prep H on my finger and I would go rescue some of it that I could reach to provide some relief. Then that became a routine because it would provide some relief at the back door for me. You can use KY jelly, or lube or other stuff to really wet your finger to go on your mission, but my choice was prep H. My lower region just wasnt getting the signal that it was time to push it on out. I felt my belly was ready and I felt my lower was ready, but even pushing I felt like I wasnt co ordinated and couldnt get the result I needed, because I was just making my face red, and not getting enough pressure into my bottom to make anything go.

My GI MD at Dartmouth Hosptial in Lebanon NH is making a documented case of me to put in the annual of reports so that others seeking the same type of help can see that other MS patients do have destruction of nerve tissue in the intestine. The lining of our intestine is almost identical to our brain, so if MS attacks the mylin or fat around the brain and eats into the nerve fibers, why cant it eat into the fat around our intestine and eat into the nerve fibers? Most wont put it together because the GI tract has its own nervous system and generally isnt well controlled by the brain, but if you consider that its been attacked the same as the brain would be...you get the answer.

Most folks take Reglan, and its normally well tolerated. Some of us get tics, twitches and grimaces from the drug and it can be permenant nerve damage, so I was tried on a whole host of meds till we had to order from over seas to get Motillium. it does the same thing as reglan, but somehow doesnt make me twitch.

Research gastroparesis. they have several forums out there with tips and tricks on how to eat better, and interventions to help. 50% of the population just takes the reglan and get on with their lives. Some folks have episodes where for 3 months its awful! and then all of a suden things get better for no reason. its like having a flair of MS only in your tummy, not in your head. Some folks have permenant damage from the attacks and have to stay on meds. I have now backed off to once a day with my meds, but wouldnt hesitate to go back up if needed.

Tremendous relief to know I wasnt weird, strange or alone. The MS team took a little longer to come on board till the GI team presented them with study after study or MS presenting in the GI tract. So, we are the pioneers in getting the MS teams to see that this stuff can nick the tummy too. You may meet with resistance, but the more folks that get documented, the more hope those behind us have.

Goodluck write me privately if you wish.

I have had to dis-impact, as well. I had a Dynamic Proctography at University of Chicago in IL, and the doctor that did the test, told me, "Everything just drops to the bottom & sits there." He said my body was shutting down, and my doctors needed to find out why.

In '06, I lost 18#s in 5 months. Just lost my appetite. I was down to 72#s at one point, up to 78#s now.

I found a web-site that lists compounding pharmacies in the US for Motillium.
I'm going to take it to my G.I. Doc and ask him to let me try it.

http://www.breastfeedingonline.com/d...shtml#ILLINOIS

(There are other States, but IL is closest to me)

I'll P.M. you privately when we return from our trip on Thursday evening.

Thank you so much for your input.

Chelle

Dejibo 07-04-2011 09:12 AM

I got a prescription for it and use a Canadian or online pharmacy I pay $18 for 100 tablets. There is no need to pay huge prices for this stuff. It comes prepackaged in blister packs and stays fresh a long time. You must have the prescription to get it tho.

My MD wrote for 90 tabs at a time, and they come 100 to a pack so remember that when asking for the script.

Let us know how it goes. :hug:

Yorkieville 07-04-2011 09:22 AM

Quote:

Originally Posted by Dejibo (Post 783706)
I got a prescription for it and use a Canadian or online pharmacy I pay $18 for 100 tablets. There is no need to pay huge prices for this stuff. It comes prepackaged in blister packs and stays fresh a long time. You must have the prescription to get it tho.

My MD wrote for 90 tabs at a time, and they come 100 to a pack so remember that when asking for the script.

Let us know how it goes. :hug:

Dejibo,

I don't have the words to thank you, properly.

I appreciate knowing I can save money, as my DH is retired. Although, this is not the retirement either of us ever expected. I spent two years in bed, in such miserable back pain, until my D.O. finally sent me to a Pain Management Clinic, and I had diagnostic nerve blocks, and one showed the pain is coming from the medial branch nerves. I don't understand, why, my former Neuro did not know about these nerves, when I told him I had the nerve blocks done. He was angry that anyone did nerve blocks on me.

DH retired young, 11 & 1/2 years ago, at the age of 57. So glad he did, because we had fun before November of '05.

I often think of when we 1st got married 38 years ago, he is nine years older than me, and my Mother was concerned that I would have to take care of him when he was older. Wish she was alive to see who is taking care of who.

Chelle

dmplaura 07-04-2011 12:29 PM

Oh my, I have THIS exact problem! I have been telling my doctor for ages "It's constipation", but it's really not.

I go MAYBE every 3-4 days if lucky, though I've sometimes reached up to 5. I don't have hard stools, in fact, my stools otherwise appear quite normal and healthy.

I noticed what you've been distinguishing Chelle... it gets to a point where the bowel just 'lets go', like it's finally so over-full, it all comes out at once. That's the ONLY time I feel truly like I've emptied my bowel.

I've done all the recommended: lots and lots of water, lots of fibre, magnesium. I tried stool softeners and bulk-forming capsules. Nothing's really made things better (it was harder stools before, now with the increase in water/fibre they seem otherwise healthy).

It's the fact that I'm only going every 3 days, if lucky, and as you describe, it seems only when the bowel's overfull that it finally lets loose. Otherwise I am bloated for days.

Maybe I should present my case to GP not as 'constipation' (which gets fluffed off) and instead as part of my intestine doesn't seem to be cooperating (or is dormant).

Yorkieville 07-04-2011 12:39 PM

Quote:

Originally Posted by dmplaura (Post 783749)
Oh my, I have THIS exact problem! I have been telling my doctor for ages "It's constipation", but it's really not.

I go MAYBE every 3-4 days if lucky, though I've sometimes reached up to 5. I don't have hard stools, in fact, my stools otherwise appear quite normal and healthy.

I noticed what you've been distinguishing Chelle... it gets to a point where the bowel just 'lets go', like it's finally so over-full, it all comes out at once. That's the ONLY time I feel truly like I've emptied my bowel.

I've done all the recommended: lots and lots of water, lots of fibre, magnesium. I tried stool softeners and bulk-forming capsules. Nothing's really made things better (it was harder stools before, now with the increase in water/fibre they seem otherwise healthy).



It's the fact that I'm only going every 3 days, if lucky, and as you describe, it seems only when the bowel's overfull that it finally lets loose. Otherwise I am bloated for days.

Maybe I should present my case to GP not as 'constipation' (which gets fluffed off) and instead as part of my intestine doesn't seem to be cooperating (or is dormant).

Read Dejibo's posts. She is a wealth of information!!!!

I feel, due to her, I may actually be able to get this issue resolved.

Do you get an "urge" to have a BM? I never get an urge. And I cannot feel after I have had one.

Well, I really had better get off of the computer, and finish packing or my DH is going to give me one of his "looks". :D

Chelle

dmplaura 07-04-2011 01:12 PM

Quote:

Originally Posted by Yorkieville (Post 783752)
Read Dejibo's posts. She is a wealth of information!!!!

I feel, due to her, I may actually be able to get this issue resolved.

Do you get an "urge" to have a BM? I never get an urge. And I cannot feel after I have had one.

Well, I really had better get off of the computer, and finish packing or my DH is going to give me one of his "looks". :D

Chelle

Dej is awesome! :hug: I'll read her post in a moment :).

The urge question... I don't quite know how to describe mine. I just am conscious of how long I've not gone (I keep a diary) and out of the blue (usually after I go out on a walk), I will feel like if I don't get to a bathroom ASAP, it's going to be messy.

Once there, then it's literally no 'involvement' on my part to go, it just goes. Rather, I don't have to put in an effort for it.

I don't really feel any less bloated or 'empty', but I know I've successfully ejected the cargo otherwise, you know?

Dejibo 07-04-2011 01:28 PM

I did not get an urge either, but knew that my belly was bloated, and I was uncomfy. I always looked bloated too. Xray showed I was full of poop! MD was impressed. He ordered laxatives and such, but I never get the "push" urge or the best way to describe mine is that even if my brain tells my bum to push, it never gets the message or its a confused message and while I can be some what effective most just sits there. I gave up long ago and started rescuing stuff. its gross, but it kept my hemmorhoids from going crazy. Material sitting on those veins of the exit gate can cause some humdinger hemmorhoids. I had a few thrombose or clot off because normally the passage of material massages the veins and helps the blood flow but when stuff sits, so does the blood.

NAsty business. I would never get the "dumping" syndrome unless I was over heated and then BOOM! without the sun or heat I just couldnt get my bowel to figure out what its job is. Like I was speaking french and my colon was speaking German. They didnt understand each other.

lefthanded 07-05-2011 03:41 PM

Internal a_n_a_l sphincter spams is perhaps my most disabling issue. However, unlike most of you, I have no colon or rectum, as they were removed in 2002 due to severe ulcerative colitis. They then reconstructed my ileum into a "j-pouch" (a reservoir to replace the colon) and reattached it to my a_n_u_s right at the sphincter (called an anastomosis).

Without a colon the stools one passes are not completely neutralized, nor are they nicely compacted and "smooth" like they are when they pass through the large intestine. This means that digestive acids and enzymes are still active, bits of undigestible fiber are present (and can be quite irritating on the way out) and because the small intestine is constantly in motion, bathroom urges are ever present. We j-pouchers have named this "inconvenience" butt-burn, because we tend to suffer severe skin breakdown from leakage.

In addition to all this, I have scar tissue and strictures built up around the anastomosis, and these lead to severe spasming of the internal a-sphincter, which in turn has caused a_n_a_l fissures to develop. If you are feeling a severe knife-like pain or burning, it is likely a fissure causing your pain. Now, add to a fresh cut, which is what a fissure is (in the most tender skin on your body), caustic stool in an imperfect colon-rectum replacement (the j-pouch) . . . you can lose entire days to the bathroom. You have a picture of my life. :) Fun? :( No!

I have been on a regimen of regular manual dilation of this internal a-sphincter for some years now, either using a dilator or a gloved digit. I use a compounded ointment containing lidocaine for pain and diltiazem for relaxing the muscle. Some people use nitroglycerine but it can cause terrible head-aches, so I opted for the diltiazem. For several years I had pretty good maintenance of my issue, but lately it has become more difficult to relax that stubborn muscle. (By the way, we do what we have to, right? Self-dilation has become so second nature, I carry a small vial of ointment and gloves in my purse at all times. I have dilated at 29,000' in a tiny airplane bathroom, in a porta-potty, and and many times in public restrooms. You do what you gotta do, right?)

The idea that there may be a herbal approach in vinpocetine is exciting to me. My surgeon's next step was to try botox, but that could render me incontinent, which means not able to leave the house (or the bathroom for that matter) until it wears off. Like I said, incontinence with loose, caustic stools can be terribly disabling, not to mention excruciatingly painful. I would be ecstatic to find some improvement . . . any improvement. I would think I had died and gone to heaven if it controlled the spasms, and the fissures could heal. I might actually be able to go hiking again . . . or even make it through a meal . . . .

missj 07-05-2011 04:03 PM

wow.
I send cyber hugs and thank you for your candidness. I can relate to much (but not all) and admit that I even wrote a haiku about this dreadful condition. I will send it via message if you are interested, just hesitant to post on the www for the w to see forever!!

jackD 07-06-2011 01:08 AM

Vinpocetine abstracts
 
Quote:

Phosphodiesterase inhibitors cause relaxation of the internal a-n-a-l sphincter in vitro.

Jones OM, Brading AF, McC Mortensen NJ.
SourceUniversity Department of Pharmacology, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract
PURPOSE: Pharmacologic treatments are gaining widespread acceptance as first-line therapy for a-n-a-l fissure. However, existing treatments have limited clinical usefulness because of side effects and incomplete healing rates.

METHODS: Fresh human surgical resection specimens containing internal a-n-a-l sphincter and rectal circular muscle were collected. Strips of smooth muscle were cut from each muscle group and mounted in a superfusion organ bath. The effects of increasing concentrations of phosphodiesterase inhibitors were evaluated.

RESULTS: All phosphodiesterase inhibitors tested caused a dose-dependent reduction in the tone of the internal a-n-a-l sphincter, with potencies as follows: vinpocentine (phosphodiesterase-1 inhibitor; 50 percent maximum inhibition concentration = 0.87 +/- 0.10 microM), erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (phosphodiesterase-2 inhibitor; 32 +/- 4.8 microM), trequinsin (phosphodiesterase-3 inhibitor; 0.28 +/- 0.041 microM), rolipram (phosphodiesterase-4 inhibitor; 63 +/- 9 microM), zaprinast (phosphodiesterase-1,5,6,9,11 inhibitor; 3 +/- 0.69 microM), and dipyridamole (phosphodiesterase-5,6,8,10,11 inhibitor; 5.5 +/- 2 microM). Although all inhibitors were also effective on rectal circular muscle strips, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, trequinsin, and rolipram were at least an order of magnitude more potent in this tissue than in the internal a-n-a-l sphincter.

CONCLUSIONS: There are several functionally important phosphodiesterases in the internal a-n-a-l sphincter and rectal circular muscle. Both adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate appear to be important in the myogenic tone of the internal a-n-a-l sphincter, and this study provides further evidence of the sphincteric specialization of this tissue. Phosphodiesterase inhibitors might represent a new therapy for the treatment of a-n-a-l fissure.


World J Urol. 2001 Nov;19(5):344-50.

Quote:

Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside.

Phosphodiesterase inhibitors cause relaxation of the internal a-n-a-l sphincter in vitro.
Jones OM, Brading AF, McC Mortensen NJ.
SourceUniversity Department of Pharmacology, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract
PURPOSE: Pharmacologic treatments are gaining widespread acceptance as first-line therapy for a-n-a-l fissure. However, existing treatments have limited clinical usefulness because of side effects and incomplete healing rates.

METHODS: Fresh human surgical resection specimens containing internal a-n-a-l sphincter and rectal circular muscle were collected. Strips of smooth muscle were cut from each muscle group and mounted in a superfusion organ bath. The effects of increasing concentrations of phosphodiesterase inhibitors were evaluated.

RESULTS: All phosphodiesterase inhibitors tested caused a dose-dependent reduction in the tone of the internal a-n-a-l sphincter, with potencies as follows: vinpocentine (phosphodiesterase-1 inhibitor; 50 percent maximum inhibition concentration = 0.87 +/- 0.10 microM), erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (phosphodiesterase-2 inhibitor; 32 +/- 4.8 microM), trequinsin (phosphodiesterase-3 inhibitor; 0.28 +/- 0.041 microM), rolipram (phosphodiesterase-4 inhibitor; 63 +/- 9 microM), zaprinast (phosphodiesterase-1,5,6,9,11 inhibitor; 3 +/- 0.69 microM), and dipyridamole (phosphodiesterase-5,6,8,10,11 inhibitor; 5.5 +/- 2 microM). Although all inhibitors were also effective on rectal circular muscle strips, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, trequinsin, and rolipram were at least an order of magnitude more potent in this tissue than in the internal a-n-a-l sphincter.

CONCLUSIONS: There are several functionally important phosphodiesterases in the internal a-n-a-l sphincter and rectal circular muscle. Both adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate appear to be important in the myogenic tone of the internal a-n-a-l sphincter, and this study provides further evidence of the sphincteric specialization of this tissue. Phosphodiesterase inhibitors might represent a new therapy for the treatment of a-n-a-l fissure.

PMID: 12006938 [PubMed - indexed for MEDLINE]


Truss MC, Stief CG, Uckert S, Becker AJ, Wefer J, Schultheiss D, Jonas U.

Urologische Klinik, Medizinische Hochschule, Hannover, Germany. truss.michael@mh-hannover.de

Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders.

We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis.

The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size.

Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction.

PMID: 11760783 [PubMed - indexed for MEDLINE]
World J Urol. 2000 Dec;18(6):439-43.

Quote:

Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder.
Truss MC, Stief CG, Uckert S, Becker AJ, Schultheiss D, Machtens S, Jonas U.

Department of Urology, Medizinische Hochschule Hannover, Germany. truss.michael@mh-hannover.de

Current pharmacological treatment modalities for urge incontinence and low compliance bladder are limited by a low clinical efficacy and the significant side effects of the standard drugs available. Previous in vitro studies indicated a possible functional relevance of the intracellular phosphodiesterase (PDE)-1 isoenzyme in the regulation of human detrusor smooth muscle contractility.

We therefore investigated the effect of the PDE-1 inhibitor vinpocetine in nonresponders to standard pharmacological therapy. In 11/19 patients (57.9%) clinical symptoms and/or urodynamic parameters were improved. Although these initial data are preliminary, they represent the first evidence that isoenzyme-selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders.

PMID: 11204266 [PubMed - indexed for MEDLINE]

Eur J Drug Metab Pharmacokinet. 1984 Apr-Jun;9(2):169-75.

Pharmacokinetics of vinpocetine and apovincaminic acid in patients with impaired renal function.
Miskolczi P, Vereczkey L, Szalay L, Göndöcs CS.

Effects of renal insufficiency on the pharmacokinetics of vinpocetine and its main metabolite, apovincaminic acid (AVA) were investigated in the present study. The elimination rate constant, half-life, clearance, area under the curve and volume of distribution were measured and compared with reported values for subjects with normal renal function. Previous investigations have shown that the elimination half life of vinpocetine was 2.54 +/- 0.48 hours and half-life of AVA was 3.66 +/- 1.56 hours in healthy volunteers after i.v. administration of 10 mg vinpocetine.

PMID: 6745306 [PubMed - indexed for MEDLINE]

Mult Scler. 2000 Feb;6(1):56-8.

Drop in relapse rate of MS by combination therapy of three different phosphodiesterase inhibitors.
Suzumura A, Nakamuro T, Tamaru T, Takayanagi T.

Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-0813, Japan.

Phosphodiesterase inhibitors (PDEIs), when used in combination, synergistically suppress TNFalpha production by various cells and also suppress experimental demyelination at very low concentrations. We conducted a pilot study to determine whether the combination of three PDEIs suppresses the relapse of MS at the usual therapeutic doses. Of the 12 relapsing remitting MS, the mean relapse rate/year dropped remarkably (from 3.08+/-3.32 to 0.92+/-1.86) after PDEI treatment. Seven out of 12 (58.3%) were relapse-free in the follow up period (499+/-142 days). The combination of three PDEIs can be safe and useful strategy for the future treatment of MS. - 58

PMID: 10694847 [PubMed - indexed for MEDLINE
Mult Scler. 1999 Apr;5(2):126-33.

Quote:

Effects of phosphodiesterase inhibitors on cytokine production by microglia.
Yoshikawa M, Suzumura A, Tamaru T, Takayanagi T, Sawada M.

Department of Neurology, Nara Medical University, Kashihara, Japan.

Type III and IV phosphodiesterase inhibitors (PDEIs) have recently been shown to suppress the production of TNF-alpha in several types of cells. In the present study, we have shown that all the types of PDEIs, from type I- to V-specific and non-specific, suppress the production of TNF-alpha by mouse microglia stimulated with lipopolysaccharide (LPS) in a dose-dependent manner. Certain combinations of three different types of PDEIs synergistically suppressed TNF-alpha production by microglia at a very low concentration (1 microM). Since some PDEIs reportedly pass through the blood-brain barrier (BBB), the combination of three PDEIs may be worth trying in neurological diseases, such as multiple sclerosis and HIV-related neurological diseases in which TNF-alpha may play a critical role. Some PDEIs also suppressed interleukin-I (IL-I) and IL-6 production by mouse microglia stimulated with LPS. In contrast, the production of IL-10, which is known to be an inhibitory cytokine, was upregulated by certain PDEIs. The suppression of TNF-alpha and induction of IL-10 were confirmed at the mRNA level by RT-PCR. PDEIs may be useful anti-inflammatory agents by downregulating inflammatory cytokines and upregulating inhibitory cytokines in the central nervous system. (CNS).

PMID: 10335522 [PubMed - indexed for MEDLINE]

SallyC 07-06-2011 11:17 AM

OK, what is the word that won't print....Duh!!! Hyphinate it..:)

lefthanded 07-06-2011 01:12 PM

Quote:

Originally Posted by SallyC (Post 784210)
OK, what is the word that won't print....Duh!!! Hyphinate it..:)

a_n_a_l
a_n_u_s

SallyC 07-06-2011 01:59 PM

Quote:

Originally Posted by lefthanded (Post 784239)
a_n_a_l
a_n_u_s

That is soooooo stuuuuuupid..:rolleyes:

They must all be A n a l retentive..:D:p:D

Yorkieville 07-07-2011 02:13 PM

Quote:

Originally Posted by dmplaura (Post 783767)
Dej is awesome! :hug: I'll read her post in a moment :).

The urge question... I don't quite know how to describe mine. I just am conscious of how long I've not gone (I keep a diary) and out of the blue (usually after I go out on a walk), I will feel like if I don't get to a bathroom ASAP, it's going to be messy.

Once there, then it's literally no 'involvement' on my part to go, it just goes. Rather, I don't have to put in an effort for it.

I don't really feel any less bloated or 'empty', but I know I've successfully ejected the cargo otherwise, you know?


Sorry for my late reply, my DH & I just got home from our trip today.

For me, I am only conscious that there is stool, pressing against the muscle, and it is uncomfortable. No urge to evacuate, so, I will gently strain, and sometimes some will pass. The straining causes the nerves in my spine to burn, and it makes my back hurt.

During these times, the stool is narrow.

Other times, if it is really full, and the stool is firm, it will force the muscle to open, but only some of the stool will pass. It is like the muscle clamps shut.


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