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Old 07-04-2011, 12:39 PM #31
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Originally Posted by dmplaura View Post
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".

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Old 07-04-2011, 01:12 PM #32
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Originally Posted by Yorkieville View Post
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".

Chelle
Dej is awesome! 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?
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Old 07-04-2011, 01:28 PM #33
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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.
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Old 07-05-2011, 03:41 PM #34
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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 . . . .
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Old 07-05-2011, 04:03 PM #35
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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!!
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Old 07-06-2011, 01:08 AM #36
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Default 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]
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Old 07-06-2011, 11:17 AM #37
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OK, what is the word that won't print....Duh!!! Hyphinate it..
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Old 07-06-2011, 01:12 PM #38
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OK, what is the word that won't print....Duh!!! Hyphinate it..
a_n_a_l
a_n_u_s
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Old 07-06-2011, 01:59 PM #39
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a_n_a_l
a_n_u_s
That is soooooo stuuuuuupid..

They must all be A n a l retentive..
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Old 07-07-2011, 02:13 PM #40
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Dej is awesome! 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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