I went to see the stem cell Dr Wed and we went over my blood work I wish I had the blood work done before treatment so I could have compared the results anyway my cholesterol is still high don't understand it eating all that chicken but the ratio for good and bad is within range my thyroid is still very low and my clotting factor is off seems I am making clots for no apparent reason my platelet numbers are high so I need to go back in 6 weeks to redo blood work asked about the sunshine he didn't know why Dr f is recommending that but said he would check into they are talking about new protocol for new patients using juicers instead of all the pills just talking right now but I would love that anyway He sold me a supplement I have been taking it for 3 days my pulse is staying in the high 70 before if it got under 100 i was happy my heart isn't pounding through my chest anymore and no xanex maybe this was all I needed all along he did say my adrenal glands weren't working right either he saw that by looking at my finger nails I have ridges I probably have forgotten somethings but as I remember them I will write I am going to start lowering the o2 pulse is 71 o2 level is 97 see how long I can go
DR report
- Thread starter Bev12452
- Start date
Bev's blood work
Hi Bev - Thanks for the report. What is he planning to do for your adrenal glands? Always, something, isn't there? Juicing is something that you can start now. Don't wait for them! It is difficult however, to be a true blue juicer because it is a lot of work if you are going to make the juices yourself. I do make my own orange juice and lemonade and I wish I had a cook or someone who would make juices for me, but I don't so I usually end up buying other kinds of juice. The supplement program is going to be modified as of February 1 when several of the supplements will be available all in one capsule. That's good news for all of us that are on the supplement program. As for your cholesterol, I think some people are just prone to having higher cholesterol levels than others. There are so many opinions out there right now about what is acceptable that I admit to being confused. Maybe, you shouldn't eat so much chicken. It does have a lot of fat in it. Switch to salmon or other fish that have the good fats in them and see if that helps. Just my two cents.
Hi Bev - Thanks for the report. What is he planning to do for your adrenal glands? Always, something, isn't there? Juicing is something that you can start now. Don't wait for them! It is difficult however, to be a true blue juicer because it is a lot of work if you are going to make the juices yourself. I do make my own orange juice and lemonade and I wish I had a cook or someone who would make juices for me, but I don't so I usually end up buying other kinds of juice. The supplement program is going to be modified as of February 1 when several of the supplements will be available all in one capsule. That's good news for all of us that are on the supplement program. As for your cholesterol, I think some people are just prone to having higher cholesterol levels than others. There are so many opinions out there right now about what is acceptable that I admit to being confused. Maybe, you shouldn't eat so much chicken. It does have a lot of fat in it. Switch to salmon or other fish that have the good fats in them and see if that helps. Just my two cents.
Bev - another cholesterol tip
Bev - I should also have mentioned that green tea helps to lower bad cholesterol. I take the capsules and I drink a cup or two a day of it. I have been to a few restaurants lately that offered it. Something, you would have never seen even a couple of years ago except in Japanese restaurants. The way we eat is changing and I might add for the better. It will take people some time to get used to better eating, but anyone can see that we were all on the fast track to nowhere with poor eating habits. Also, in a post from Harv the other day, he mentioned several very healthful juices that you can buy.
Bev - I should also have mentioned that green tea helps to lower bad cholesterol. I take the capsules and I drink a cup or two a day of it. I have been to a few restaurants lately that offered it. Something, you would have never seen even a couple of years ago except in Japanese restaurants. The way we eat is changing and I might add for the better. It will take people some time to get used to better eating, but anyone can see that we were all on the fast track to nowhere with poor eating habits. Also, in a post from Harv the other day, he mentioned several very healthful juices that you can buy.
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newest update
for my Birthday I treated myself to an appointment with the herbalist she did strenth testing on me and discovered that I am lacking in all the major vitimins and minerials it seems my small colon is not absorbing the supplements so I have started taking 2 ounces of Noni Juice in the morning and 2 tablets of gaba along with alll the other things we take also started on an hrt that the DR in tampa suggested so now I wait to see if this will make any changes in my recovery yesterday I think I overdosed on the estrogen boy did I have some hot flashes today is better but I did call to find an easier way to administer they said take 4 drops sunlingual well I had it runing down my face down the bottle, the office staff laughed at my story but were kind enough to give me a different compounding pharmacy well thats all for today from the forest hope everyone is having a great day
for my Birthday I treated myself to an appointment with the herbalist she did strenth testing on me and discovered that I am lacking in all the major vitimins and minerials it seems my small colon is not absorbing the supplements so I have started taking 2 ounces of Noni Juice in the morning and 2 tablets of gaba along with alll the other things we take also started on an hrt that the DR in tampa suggested so now I wait to see if this will make any changes in my recovery yesterday I think I overdosed on the estrogen boy did I have some hot flashes today is better but I did call to find an easier way to administer they said take 4 drops sunlingual well I had it runing down my face down the bottle, the office staff laughed at my story but were kind enough to give me a different compounding pharmacy well thats all for today from the forest hope everyone is having a great day
Bev's birthday bash
Bev - All this time you have been faithfully swallowing a pharmacy full of supplements and they weren't absorbing. That really sucks. I hope the juice will help. I won't comment on better ways to spend your birthday. You did get a good present if the doctor figured out what was going on.
Bev - All this time you have been faithfully swallowing a pharmacy full of supplements and they weren't absorbing. That really sucks. I hope the juice will help. I won't comment on better ways to spend your birthday. You did get a good present if the doctor figured out what was going on.
another visit to the DR
I went to the DR in Tampa and he said how much better I looked now the group that I was with in San Diego know how vain I am so th Drs remarks made me feel alot better he said my color was real good which means my body is getting enough o2 as far as the questions I had first the weight I did follow some of the suggestions from the group and did put on 6 Pd's but he said the weight itself wasn't the problem it seems my body is using muscle mass to feed similar to cancer patients so I am trying a new form of amino acid it is in crystal form and dissolves right in your mouth started taking a b12 supplement so my body will absorb and a glandular lung formula the nutritionist also suggested I try a mycelllized vitimin a I showed her the supplement list and she said they were all good but was surprised it didn't have more things aimed toward lungs so vitamin a at the highest dose for 7 days than regular dose I did have an IV bag full of vitamins and I did feel alot better yesterday I even felt like eating the high pulse is due to my anxiety and also my adrenal glands hopefully it will all start to even out I figured out last night even if my cells don't work I have learned so much about how my body works and what each thing does and how to treat it has truly been a learning experience and I have met some of the greatest people I toast all of you tonight with my 32 ounces of water along with my handful of supplements have a great weekend
I went to the DR in Tampa and he said how much better I looked now the group that I was with in San Diego know how vain I am so th Drs remarks made me feel alot better he said my color was real good which means my body is getting enough o2 as far as the questions I had first the weight I did follow some of the suggestions from the group and did put on 6 Pd's but he said the weight itself wasn't the problem it seems my body is using muscle mass to feed similar to cancer patients so I am trying a new form of amino acid it is in crystal form and dissolves right in your mouth started taking a b12 supplement so my body will absorb and a glandular lung formula the nutritionist also suggested I try a mycelllized vitimin a I showed her the supplement list and she said they were all good but was surprised it didn't have more things aimed toward lungs so vitamin a at the highest dose for 7 days than regular dose I did have an IV bag full of vitamins and I did feel alot better yesterday I even felt like eating the high pulse is due to my anxiety and also my adrenal glands hopefully it will all start to even out I figured out last night even if my cells don't work I have learned so much about how my body works and what each thing does and how to treat it has truly been a learning experience and I have met some of the greatest people I toast all of you tonight with my 32 ounces of water along with my handful of supplements have a great weekend
Bev's battle with the no bulge
Wow, Bev what a learning experience is right. How much is the maximum dosage he recommended of Vitamin A? The supplement program is a general one geared for cell engraftment. Vitamin A can also be tricky (and dangerous in large doses) so it is best that you did have the doctor help you with this. After the first 6 months, I made personal changes to the supplement program that were more geared for my condition and I think this is important for each person to do. We will have information concerning this very soon and it may be helpful to those that are continuing to take supplements. I think the aminos are real important. I am glad you put on 6 pounds. That actually is quite a bit for the short time since you posted about needing to gain weight. It's good news about your coloring too. That really is a significant sign that things are going better on the inside. Really good to hear this. Thanks for posting.
Wow, Bev what a learning experience is right. How much is the maximum dosage he recommended of Vitamin A? The supplement program is a general one geared for cell engraftment. Vitamin A can also be tricky (and dangerous in large doses) so it is best that you did have the doctor help you with this. After the first 6 months, I made personal changes to the supplement program that were more geared for my condition and I think this is important for each person to do. We will have information concerning this very soon and it may be helpful to those that are continuing to take supplements. I think the aminos are real important. I am glad you put on 6 pounds. That actually is quite a bit for the short time since you posted about needing to gain weight. It's good news about your coloring too. That really is a significant sign that things are going better on the inside. Really good to hear this. Thanks for posting.
vitamin a
I have emailed the nutritionist concerning the maximum dosage she would recommend as soon as I get a response I will send it out the vitamin a is liquid and one drop is 5000 I/u that is the recommended daily use I forgot the best news I can go out in the sun 10 minutes twice a day I was so happy I rode home from Tampa with the sun roof open and windows down maybe that is what made for the great attitude anyway have a great day
I have emailed the nutritionist concerning the maximum dosage she would recommend as soon as I get a response I will send it out the vitamin a is liquid and one drop is 5000 I/u that is the recommended daily use I forgot the best news I can go out in the sun 10 minutes twice a day I was so happy I rode home from Tampa with the sun roof open and windows down maybe that is what made for the great attitude anyway have a great day
vitimin a
I spoke with the nutritionist yesterday concerning the amount of vitamin a she recommends 4 drops per day for 7 days and than 1 drop per day the vitamin a is 5000 IU per drop so I am going to try will let you all know if anything happens I tried to go through all t posts to find the individuals who had given me such great advice about nutrition I have increased my potassium and my pulse seems to be slowing down so thank you also the B 12 thanks for that info it sure doesn't taste as good as a hamburger but I feel better everyday my 02 while sitting stays around 95 but drops dramatically upon movement which goes to show I need to move more but all in all feeling good thanks to you all having a great day in sunny Florida hope everyone is enjoying spring
I spoke with the nutritionist yesterday concerning the amount of vitamin a she recommends 4 drops per day for 7 days and than 1 drop per day the vitamin a is 5000 IU per drop so I am going to try will let you all know if anything happens I tried to go through all t posts to find the individuals who had given me such great advice about nutrition I have increased my potassium and my pulse seems to be slowing down so thank you also the B 12 thanks for that info it sure doesn't taste as good as a hamburger but I feel better everyday my 02 while sitting stays around 95 but drops dramatically upon movement which goes to show I need to move more but all in all feeling good thanks to you all having a great day in sunny Florida hope everyone is enjoying spring
Vitamin A info
I am assuming that your nutritionist meant for you to do the 7 day increased dosage just once. It is very high and vitamin A can be damaging although several studies are also showing that it may be beneficial to the growth of alveoli in the lungs. Is this what you are trying to accomplish? I do think a little more exertion and exericise on a daily basis and of course the PowerLung (nag, nag, nag) may help you not drop your sats so quickly when you try to get up and do something. Sometimes, it gets discouraging not seeing quick progress, but if you keep at it all, you will reap the benefits later on. You have such a good attitude Bev and that comes from feeling better too. Keep up your good work and your quest to feel better.
I am assuming that your nutritionist meant for you to do the 7 day increased dosage just once. It is very high and vitamin A can be damaging although several studies are also showing that it may be beneficial to the growth of alveoli in the lungs. Is this what you are trying to accomplish? I do think a little more exertion and exericise on a daily basis and of course the PowerLung (nag, nag, nag) may help you not drop your sats so quickly when you try to get up and do something. Sometimes, it gets discouraging not seeing quick progress, but if you keep at it all, you will reap the benefits later on. You have such a good attitude Bev and that comes from feeling better too. Keep up your good work and your quest to feel better.
Pottassium (Bev)
Delighted the KCL is helping Bev. It would help to get your whole blood pottassium checked. Routine tests check serum levels, but only 5% of KCL is in serum. My German doctor explained it to me, so I'm just passing on his wisdom! How much are you taking? I was recommended 600mg daily and it has lowered my blood pressure and pulse rate. It's important to have regular blood checks tho.
Regards from a cold wet Ireland!
Anne.
Delighted the KCL is helping Bev. It would help to get your whole blood pottassium checked. Routine tests check serum levels, but only 5% of KCL is in serum. My German doctor explained it to me, so I'm just passing on his wisdom! How much are you taking? I was recommended 600mg daily and it has lowered my blood pressure and pulse rate. It's important to have regular blood checks tho.
Regards from a cold wet Ireland!
Anne.
Hi Barb
I was looking over your latest posts and saw that your sats dropped when you'd get up to do things; but stayed about 95 when you were just sitting. I don't know if I've ever asked you this before---but had you ever gone through pulmonary rehab? I only ask because I was in the same situation after contracting that heart virus. But after I attended the rehab sessions I was amazed at what I could do !!
I know I went in thinking " I have a hard enough time just walking around the house, and they want me to exercise?????!!!!!" But after rehab, I only needed my O2 on the treadmill, at 2lpm. I didn't need it on any of the other exercise equipment!!!!! AND---I could go up and down my basement steps without oxygen!!!!! Also,----I have a very hard time maintaining my weight and I just knew if I exercised I'd drop those pounds I'd worked so hard to put back on after my illness. But I exercised and did lose some weight. But, after keeping up the exercise at least 3 times a week at home, the muscle mass I put on helped put some pounds back on.
I had stopped exercising for about 8 months this past year so that I could put the weight back on and feel better. I was also very active taking my friend Pete to his appointments and getting him out of his house to help him with his depression. (After the zillions of things I tried to keep weight on, I finally found what worked. I have ONE beer a day!!!!) Now that I have gained enough back---I'm back to exercising.
I know that I lost some of my muscle when I went on that 8 month strike. But now that I've started back exercising----I can do a lot better.
I know it's hard to have such a hard time breathing and being SOB---but I just don't want to do nothing. I want to be able to do my gardening again without having to rest ever 2 minutes!!! I want to be able to walk around the block with my grandkids again.
It was a dilema---exercise and lose the weight; or don't exercise and lose the ability to do things comfortably. But----the beer worked and now I can go back to my old exercise routine. It'll take a few weeks before I'm back where I was---but I'll get there.
I'm sure it's hard having to change everything----your diet and the supplements. But if it works----then that's great. I got into vitamins and supplements about 16 years ago and just stuck with it. I have NO idea how I'd feel if I didn't take them. People told me how much better I looked after making it a habit to exercise and maintain the supplements; and they didn't even KNOW I was exercising or taking supplements!!!! Maybe that will be a bonus for me when I go to get my cells.
You can do it. Just take a step at a time and work up from there.
I was looking over your latest posts and saw that your sats dropped when you'd get up to do things; but stayed about 95 when you were just sitting. I don't know if I've ever asked you this before---but had you ever gone through pulmonary rehab? I only ask because I was in the same situation after contracting that heart virus. But after I attended the rehab sessions I was amazed at what I could do !!
I know I went in thinking " I have a hard enough time just walking around the house, and they want me to exercise?????!!!!!" But after rehab, I only needed my O2 on the treadmill, at 2lpm. I didn't need it on any of the other exercise equipment!!!!! AND---I could go up and down my basement steps without oxygen!!!!! Also,----I have a very hard time maintaining my weight and I just knew if I exercised I'd drop those pounds I'd worked so hard to put back on after my illness. But I exercised and did lose some weight. But, after keeping up the exercise at least 3 times a week at home, the muscle mass I put on helped put some pounds back on.
I had stopped exercising for about 8 months this past year so that I could put the weight back on and feel better. I was also very active taking my friend Pete to his appointments and getting him out of his house to help him with his depression. (After the zillions of things I tried to keep weight on, I finally found what worked. I have ONE beer a day!!!!) Now that I have gained enough back---I'm back to exercising.
I know that I lost some of my muscle when I went on that 8 month strike. But now that I've started back exercising----I can do a lot better.
I know it's hard to have such a hard time breathing and being SOB---but I just don't want to do nothing. I want to be able to do my gardening again without having to rest ever 2 minutes!!! I want to be able to walk around the block with my grandkids again.
It was a dilema---exercise and lose the weight; or don't exercise and lose the ability to do things comfortably. But----the beer worked and now I can go back to my old exercise routine. It'll take a few weeks before I'm back where I was---but I'll get there.
I'm sure it's hard having to change everything----your diet and the supplements. But if it works----then that's great. I got into vitamins and supplements about 16 years ago and just stuck with it. I have NO idea how I'd feel if I didn't take them. People told me how much better I looked after making it a habit to exercise and maintain the supplements; and they didn't even KNOW I was exercising or taking supplements!!!! Maybe that will be a bonus for me when I go to get my cells.
You can do it. Just take a step at a time and work up from there.
Connie Golden
New member
More on Vitamin A
Dear Bev and Barb,
Last week a business associate told me that his father had suffered with emphasema for 25 years and at one point the family was preparing to assist in his death when they came upon some research using massive dosages of Vitamin A on monkeys. They decided to try it with the assistance of a doctor who closely monitored the level of toxicity through frequent blood tests. He said this made possible new growth of alveoli. His father was able to live a full life; remarried; started a new business and passed away last year at 94. He said he knew he had at least three rounds of treatment and he is positive it cured and maintained his fathers health.
I'll be following your progress Bev.
All best, Connie
Dear Bev and Barb,
Last week a business associate told me that his father had suffered with emphasema for 25 years and at one point the family was preparing to assist in his death when they came upon some research using massive dosages of Vitamin A on monkeys. They decided to try it with the assistance of a doctor who closely monitored the level of toxicity through frequent blood tests. He said this made possible new growth of alveoli. His father was able to live a full life; remarried; started a new business and passed away last year at 94. He said he knew he had at least three rounds of treatment and he is positive it cured and maintained his fathers health.
I'll be following your progress Bev.
All best, Connie
Retinoic acid
Connie - I believe every word of what you wrote. There are numerous clinicals going on using retinoic acid and from the people I have talked to that were in them, they felt great while getting the treatment. I have no idea what on earth is taking so long to figure it all out, but these same clinicals seem to be repeated over and over again. Drs. Massaro and Massaro did some research that showed great promise with alveoli regrowth. So why is this possible life saving treatment not available? I don't have the answer. High doses of vitamin A can damage your liver, but controlled therapy like you mention saved the man's life. The possible side effect he would have suffered without the treatment was death. Makes you wonder, doesn't it?
Connie - I believe every word of what you wrote. There are numerous clinicals going on using retinoic acid and from the people I have talked to that were in them, they felt great while getting the treatment. I have no idea what on earth is taking so long to figure it all out, but these same clinicals seem to be repeated over and over again. Drs. Massaro and Massaro did some research that showed great promise with alveoli regrowth. So why is this possible life saving treatment not available? I don't have the answer. High doses of vitamin A can damage your liver, but controlled therapy like you mention saved the man's life. The possible side effect he would have suffered without the treatment was death. Makes you wonder, doesn't it?
Mysty 119
I had the same symptoms as far as desaturating and I spent 6 months in pulmo rehab which did nothing for my destauration. It made me able to do more but I still needed oxygen. Not everyone has the same type of emphysema. I know people who are far shorter of breath than I am, have the same degree of lung function but and don't need oxygen because their O2 stays above 95 at all times. It's a bizarre disease.
I had the same symptoms as far as desaturating and I spent 6 months in pulmo rehab which did nothing for my destauration. It made me able to do more but I still needed oxygen. Not everyone has the same type of emphysema. I know people who are far shorter of breath than I am, have the same degree of lung function but and don't need oxygen because their O2 stays above 95 at all times. It's a bizarre disease.
roflumilast(vitamin A
National Heart and Lung Institute, Imperial College, Dovehouse St., London SW3, UK. f.chung@imperial.ac.uk
Phosphodiesterases hydrolyse intracellular cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) into inactive 5' monophosphates, and exist as 11 families. They are found in a variety of inflammatory and structural cells. Inhibitors of PDEs allow the elevation of cAMP and cGMP which lead to a variety of cellular effects including airway smooth muscle relaxation and inhibition of cellular inflammation or of immune responses. PDE4 inhibitors specifically prevent the hydrolysis of cAMP, and PDE4 isozymes are present in inflammatory cells. Selective PDE4 inhibitors have broad spectrum anti-inflammatory effects such as inhibition of cell trafficking, cytokine and chemokine release from inflammatory cells, such as neutrophils, eosinophils, macrophages and T cells. The second generation PDE4 inhibitors, cilomilast and roflumilast, have reached clinical trial stage and have some demonstrable beneficial effects in asthma and chronic obstructive pulmonary disease (COPD). The effectiveness of these PDE4 inhibitors may be limited by their clinical potency using doses that have minimal effects on nausea and vomiting. Topical administration of PDE4 inhibitors may provide a wider effective to side-effect profile. Development of inhibitors of other PDE classes, combined with PDE4 inhibition, may be another way forward. PDE5 is an inactivator of cGMP and may have beneficial effects on hypoxic pulmonary hypertension and vascular remodelling. PDE3 and PDE7 are other cAMP specific inactivators of cAMP. PDE7 is involved in T cell activation and a dual PDE4-PDE7 inhibitor may be more effective in asthma and COPD. A dual PDE3-PDE4 compound may provide more bronchodilator and bronchoprotective effect in addition to the beneficial PDE4 effects.
Medical Clinic I, Department of Pneumology and Allergy, Friedrich-Schiller-University, Erlanger Allee 101, D-07740 Jena, Germany. CLAUS.Kroegel@med.uni-jena.de
Phosphodiesterase-4 (PDE4) is an important cAMP-metabolising enzyme in immune and inflammatory cells, airway smooth muscle and pulmonary nerves. The phosphodiesterase 4 (PDE4) enzyme plays a significant role in modulating the activity of cAMP, an important second messenger that mediates the relaxation of airway smooth muscle and suppresses inflammatory cell function, thereby attenuating the inflammatory response. Selective inhibitors of this enzyme show a broad spectrum of activity in animal models of COPD and asthma. These drugs block the hydrolysis of cAMP via inhibition of PDE4 and are attractive candidates for novel anti-inflammatory drugs. At present, two second-generation PDE4 inhibitors for the treatment of COPD and asthma patients are being tested in clinical Phase III trials. The most advanced compound is the orally active, selective PDE4 inhibitor cilomilast (Ariflo, SB-207499, cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]-cyclohexanecarboxylic acid; GlaxoSmithKline). Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilast suppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo. It is orally active and may be effective in the treatment of asthma and COPD; however, complete assessment of the therapeutic value of this novel compound class must await the outcome of longer-term clinical trials. This review presents a summary of the preclinical and clinical profile of cilomilast in patients with COPD.
PMID: 17155857 [PubMed - indexed for MEDLINE
National Heart and Lung Institute, Imperial College, Dovehouse St., London SW3, UK. f.chung@imperial.ac.uk
Phosphodiesterases hydrolyse intracellular cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) into inactive 5' monophosphates, and exist as 11 families. They are found in a variety of inflammatory and structural cells. Inhibitors of PDEs allow the elevation of cAMP and cGMP which lead to a variety of cellular effects including airway smooth muscle relaxation and inhibition of cellular inflammation or of immune responses. PDE4 inhibitors specifically prevent the hydrolysis of cAMP, and PDE4 isozymes are present in inflammatory cells. Selective PDE4 inhibitors have broad spectrum anti-inflammatory effects such as inhibition of cell trafficking, cytokine and chemokine release from inflammatory cells, such as neutrophils, eosinophils, macrophages and T cells. The second generation PDE4 inhibitors, cilomilast and roflumilast, have reached clinical trial stage and have some demonstrable beneficial effects in asthma and chronic obstructive pulmonary disease (COPD). The effectiveness of these PDE4 inhibitors may be limited by their clinical potency using doses that have minimal effects on nausea and vomiting. Topical administration of PDE4 inhibitors may provide a wider effective to side-effect profile. Development of inhibitors of other PDE classes, combined with PDE4 inhibition, may be another way forward. PDE5 is an inactivator of cGMP and may have beneficial effects on hypoxic pulmonary hypertension and vascular remodelling. PDE3 and PDE7 are other cAMP specific inactivators of cAMP. PDE7 is involved in T cell activation and a dual PDE4-PDE7 inhibitor may be more effective in asthma and COPD. A dual PDE3-PDE4 compound may provide more bronchodilator and bronchoprotective effect in addition to the beneficial PDE4 effects.
Medical Clinic I, Department of Pneumology and Allergy, Friedrich-Schiller-University, Erlanger Allee 101, D-07740 Jena, Germany. CLAUS.Kroegel@med.uni-jena.de
Phosphodiesterase-4 (PDE4) is an important cAMP-metabolising enzyme in immune and inflammatory cells, airway smooth muscle and pulmonary nerves. The phosphodiesterase 4 (PDE4) enzyme plays a significant role in modulating the activity of cAMP, an important second messenger that mediates the relaxation of airway smooth muscle and suppresses inflammatory cell function, thereby attenuating the inflammatory response. Selective inhibitors of this enzyme show a broad spectrum of activity in animal models of COPD and asthma. These drugs block the hydrolysis of cAMP via inhibition of PDE4 and are attractive candidates for novel anti-inflammatory drugs. At present, two second-generation PDE4 inhibitors for the treatment of COPD and asthma patients are being tested in clinical Phase III trials. The most advanced compound is the orally active, selective PDE4 inhibitor cilomilast (Ariflo, SB-207499, cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]-cyclohexanecarboxylic acid; GlaxoSmithKline). Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilast suppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo. It is orally active and may be effective in the treatment of asthma and COPD; however, complete assessment of the therapeutic value of this novel compound class must await the outcome of longer-term clinical trials. This review presents a summary of the preclinical and clinical profile of cilomilast in patients with COPD.
PMID: 17155857 [PubMed - indexed for MEDLINE