October 31, 2019
Lieel Icos Cialis tadalafil 80mg and 100mg tablets
The Therapeutic Goods Administration (TGA) has tested products labelled
Lieel Icos Cialis tadalafil 80mg and 100mg tablets (as compared to Lilly
on genuine Cialis tablet products) and found that:Tadalafil powder half life
Lieel Icos Cialis tadalafil: image of grey box packagingthe tablets did not contain the stated substance tadalafil.
the tablets contain the undeclared substance sildenafil.
consumers are advised that sildenafil is a prescription-only medicine.
The supply of Lieel Icos Cialis 80mg and 100mg tadalafil tablets is illegal.
Lieel Icos Cialis tadalafil 80mg and 100mg tablets have not been assessed by the TGA for quality, safety or efficacy as required under Australian legislation, and the place of manufacture is not approved by the TGA.
Lieel Icos Cialis tadalafil: image of blue box packagingTGA investigations have shown that a number of people in Australia may have bought the products online.
The TGA is working with Australian Customs and Border Protection Service (ACBPS) to help stop future shipments of Lieel Icos Cialis 80mg and 100mg tadalafil tablets from entering Australia.
If these tablets are found at the border by ACBPS they will be seized and destroyed.
The TGA is advising consumers to exercise extreme caution when purchasing medicines from unknown overseas Internet sites. Products purchased over the Internet:
Lieel Icos Cialis tadalafil: image of grey box packagingthe tablets did not contain the stated substance tadalafil.
the tablets contain the undeclared substance sildenafil.
consumers are advised that sildenafil is a prescription-only medicine.
The supply of Lieel Icos Cialis 80mg and 100mg tadalafil tablets is illegal.
Lieel Icos Cialis tadalafil 80mg and 100mg tablets have not been assessed by the TGA for quality, safety or efficacy as required under Australian legislation, and the place of manufacture is not approved by the TGA.
Lieel Icos Cialis tadalafil: image of blue box packagingTGA investigations have shown that a number of people in Australia may have bought the products online.
The TGA is working with Australian Customs and Border Protection Service (ACBPS) to help stop future shipments of Lieel Icos Cialis 80mg and 100mg tadalafil tablets from entering Australia.
If these tablets are found at the border by ACBPS they will be seized and destroyed.
The TGA is advising consumers to exercise extreme caution when purchasing medicines from unknown overseas Internet sites. Products purchased over the Internet:
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What's right for me, Sildenafil or Tadalafil?
If you’re considering medication to improve your erections and sexual
experiences, you've probably heard about the two most popular active
ingredients, Sildenafil and Tadalafil. Sildenafil is the active
ingredient popularized by the brand Viagra and is designed to last 4-6
hours. Tadalafil is the active ingredient in Cialis and designed to last
24-36 hours.
These medicines have a lot in common, including a success rate of more than 80 percent. They’ve both been well researched for decades, so you may be wondering which one will give you the best results.buyaas Tadalafil
The 4 things you should know when making your decision.
1 - Consider your plans
When your evening plans with your special someone include dining, it’s important to remember that food can impact how effectively your body absorbs medication. Sildenafil & Tadalafil pills works best on an empty stomach, so it may not be the preferred choice for a night that includes dinner or cocktails. Most troublesome are fatty meals are also a no-no because they can slow the onset of the drug’s active ingredient, meaning you’ll need to delay intercourse. That is one of the main reasons people are choosing chewable tablets that disintegrate in your mouth that are now available at Bluechew.
2 - Timing is everything.
If you’ll be spending more than an evening with your partner and don't know when the timing is going to be right, you may prefer a drug that has a longer window of opportunity. Tadalafil remains in the body longer, as long as 36 hours in most cases, so there’s no need to rush your time together. This is a big plus, because anxiety and nervousness also can cause Erectile Dysfunction (ED) even when the blood flow is working just fine.
Sildenafil, however, has a short four- to six-hour active time frame, which means you’ll need to plan your time carefully to avoid it wearing off before you need it. Traditionally men have reported Tadalafil working faster than Sildenafil, but with chewables both of them work up to twice as fast as pills, so there is not much to worry about if you choose Bluechew.
3 - Daily dosing or on demand.
For men that want to be able to have sex at any time, Tadalafil might be the better choice. It’s available in lower dose tablets ranging from 2.5 mg. to 20 mg. and advised to be taken daily. Since it stays in your system for 24-36 hours, it gives you more opportunities for spontaneous intercourse whenever you and your partner are in the mood.
Sildenafil, on the other hand, is prescribed for use as needed. It generally takes about an hour before becoming effective in pill, so a little extra patience (and planning) must be taken into consideration. With chewables that hour is greatly reduced to be closer to 30-40 minutes. It also has variable dosing depending on the patient's needs, from 25 mg. to 100 mg., but it wears off after four to six hours.
4 - Cost is always a factor
Since both medications molecules are off patent, the cost has been reduced considerably from their entry into the market. This is very good news because it shouldn't cost a fortune to be intimate with your partner. Your particular prescription will be based on the strength of the drug, so, obviously, the higher the dosage, the higher the price will be for you. At Bluechew we try to keep the price reasonable by never charging for a doctors appointment and patient support.
These medicines have a lot in common, including a success rate of more than 80 percent. They’ve both been well researched for decades, so you may be wondering which one will give you the best results.buyaas Tadalafil
The 4 things you should know when making your decision.
1 - Consider your plans
When your evening plans with your special someone include dining, it’s important to remember that food can impact how effectively your body absorbs medication. Sildenafil & Tadalafil pills works best on an empty stomach, so it may not be the preferred choice for a night that includes dinner or cocktails. Most troublesome are fatty meals are also a no-no because they can slow the onset of the drug’s active ingredient, meaning you’ll need to delay intercourse. That is one of the main reasons people are choosing chewable tablets that disintegrate in your mouth that are now available at Bluechew.
2 - Timing is everything.
If you’ll be spending more than an evening with your partner and don't know when the timing is going to be right, you may prefer a drug that has a longer window of opportunity. Tadalafil remains in the body longer, as long as 36 hours in most cases, so there’s no need to rush your time together. This is a big plus, because anxiety and nervousness also can cause Erectile Dysfunction (ED) even when the blood flow is working just fine.
Sildenafil, however, has a short four- to six-hour active time frame, which means you’ll need to plan your time carefully to avoid it wearing off before you need it. Traditionally men have reported Tadalafil working faster than Sildenafil, but with chewables both of them work up to twice as fast as pills, so there is not much to worry about if you choose Bluechew.
3 - Daily dosing or on demand.
For men that want to be able to have sex at any time, Tadalafil might be the better choice. It’s available in lower dose tablets ranging from 2.5 mg. to 20 mg. and advised to be taken daily. Since it stays in your system for 24-36 hours, it gives you more opportunities for spontaneous intercourse whenever you and your partner are in the mood.
Sildenafil, on the other hand, is prescribed for use as needed. It generally takes about an hour before becoming effective in pill, so a little extra patience (and planning) must be taken into consideration. With chewables that hour is greatly reduced to be closer to 30-40 minutes. It also has variable dosing depending on the patient's needs, from 25 mg. to 100 mg., but it wears off after four to six hours.
4 - Cost is always a factor
Since both medications molecules are off patent, the cost has been reduced considerably from their entry into the market. This is very good news because it shouldn't cost a fortune to be intimate with your partner. Your particular prescription will be based on the strength of the drug, so, obviously, the higher the dosage, the higher the price will be for you. At Bluechew we try to keep the price reasonable by never charging for a doctors appointment and patient support.
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tadalafil for treatment of male erectile dysfunction held invalid
In order to clear the way for the marketing of their own products
Actavis, Teva and Mylan applied to revoke an Icos/ Lilly patent directed
at the treatment of sexual dysfunction by the administration of a dose
of no more than 5mg tadalafil per day. They argued that it would have
been obvious for the skilled team to take tadalafil forward into a
routine pre-clinical and clinical trial programme to assess its use as
an oral treatment for sexual dysfunction. In the course of that
programme, a 5mg daily dose of tadalafil would be used in patients and
it would reveal the invention, that a 5mg daily dose is a safe,
tolerable and effective treatment.Tadalafil powder dosage
Lilly argued the case was really one of "obvious to try†and that this could only lead to a finding of invalidity if the skilled team would consider that the programme had a fair prospect of success. This they disputed because, at the start of the programme, the skilled team would have had no idea whether or not a 5mg daily dose of tadalafil would be a safe, tolerable and effective treatment of sexual dysfunction, still less that it would be both efficacious and have minimal related side effects.
The trial judge agreed with Lilly that the patent was not invalid for obviousness. He found that the skilled team would embark on the project with a reasonable expectation of success in establishing tadalafil as a safe, tolerable and effective treatment, but it would not have been able to predict that the 5mg / day dose would be effective.
The Court of Appeal held this was not a case in which the skilled team would be faced with a series of parallel avenues of study and would not have any expectation that any one of those avenues would prove fruitful or be more likely to prove fruitful than any other. Nor was it a case where most or even some of the avenues of investigation would not lead to the invention. Instead it was a case where the two possibilities of on demand and daily dosing would both be addressed in light of the earlier routine work, and where each would be very likely to lead the skilled team to the invention.
The judge wrongly attached weight to the fact that a dose of 5mg was considerably less than the 50mg dose (disclosed in the prior art) which would be used in Phase IIa efficacy test, and to the fact that a dose of 5mg would not be chosen for the routine first dose ranging study in Phase IIb. The Court of Appeal noted, however, that the two parts of Phase II clinical trials have different purposes. Phase IIa is designed to provide proof of concept and is generally carried out at one dose selected to be high enough to provide the best chance of showing a positive effect while not causing serious side effects. Phase IIb is carried out at different doses chosen to provide an understanding about the dose response relationship. Although a dose of 5mg would not be chosen for the first study in Phase IIb, the skilled but uninventive team would very likely investigate it thereafter. In the course of this it was very likely that they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention.
The judge had therefore fallen into error. If the only thing driving the skilled team to test the 5mg dose was its level of expectation that a 5mg dose might be effective, expectation of success as to efficacy would be highly material. However, phase IIb clinical tests are conducted with a separate objective, namely to identify a dose response. The absence of an expectation of success as to efficacy was, in these particular circumstances, not relevant.
Although the skilled team would be surprised by the result, namely efficacy at 5mg/day, such a finding would be arrived at by the standard, routine enquiries into dose response which are required by Phase IIb clinical trials. It followed that the surprising result, once uncovered, did not make these routine enquiries inventive.
Expectation of success, if relevant at all, should come in before making the decision on what the skilled team would do. If the skilled team had no expectation of success, that might be a reason why they would not undertake the step in question. But having come to the conclusion that they would, there was no further need to examine an expectation of success.
Lilly argued the case was really one of "obvious to try†and that this could only lead to a finding of invalidity if the skilled team would consider that the programme had a fair prospect of success. This they disputed because, at the start of the programme, the skilled team would have had no idea whether or not a 5mg daily dose of tadalafil would be a safe, tolerable and effective treatment of sexual dysfunction, still less that it would be both efficacious and have minimal related side effects.
The trial judge agreed with Lilly that the patent was not invalid for obviousness. He found that the skilled team would embark on the project with a reasonable expectation of success in establishing tadalafil as a safe, tolerable and effective treatment, but it would not have been able to predict that the 5mg / day dose would be effective.
The Court of Appeal held this was not a case in which the skilled team would be faced with a series of parallel avenues of study and would not have any expectation that any one of those avenues would prove fruitful or be more likely to prove fruitful than any other. Nor was it a case where most or even some of the avenues of investigation would not lead to the invention. Instead it was a case where the two possibilities of on demand and daily dosing would both be addressed in light of the earlier routine work, and where each would be very likely to lead the skilled team to the invention.
The judge wrongly attached weight to the fact that a dose of 5mg was considerably less than the 50mg dose (disclosed in the prior art) which would be used in Phase IIa efficacy test, and to the fact that a dose of 5mg would not be chosen for the routine first dose ranging study in Phase IIb. The Court of Appeal noted, however, that the two parts of Phase II clinical trials have different purposes. Phase IIa is designed to provide proof of concept and is generally carried out at one dose selected to be high enough to provide the best chance of showing a positive effect while not causing serious side effects. Phase IIb is carried out at different doses chosen to provide an understanding about the dose response relationship. Although a dose of 5mg would not be chosen for the first study in Phase IIb, the skilled but uninventive team would very likely investigate it thereafter. In the course of this it was very likely that they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention.
The judge had therefore fallen into error. If the only thing driving the skilled team to test the 5mg dose was its level of expectation that a 5mg dose might be effective, expectation of success as to efficacy would be highly material. However, phase IIb clinical tests are conducted with a separate objective, namely to identify a dose response. The absence of an expectation of success as to efficacy was, in these particular circumstances, not relevant.
Although the skilled team would be surprised by the result, namely efficacy at 5mg/day, such a finding would be arrived at by the standard, routine enquiries into dose response which are required by Phase IIb clinical trials. It followed that the surprising result, once uncovered, did not make these routine enquiries inventive.
Expectation of success, if relevant at all, should come in before making the decision on what the skilled team would do. If the skilled team had no expectation of success, that might be a reason why they would not undertake the step in question. But having come to the conclusion that they would, there was no further need to examine an expectation of success.
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Amino Tadanafil Powder Sexual pills Amino Tadalafil Powder
Tadalafil is a PDE5 inhibitor marketed in pill form for treating
erectile dysfunction (ED) under the name Tadalafil, and under the name
Adcirca for the treatment of pulmonary arterial hypertension.buyaas Tadalafil powder
Tadalafil's pharmacologic distinction is its longer half-life (17.50 hours) resulting in longer duration of action, and so partly responsible for "The Weekend Pill" sobriquet. Furthermore, the longer half-life is the basis for current investigation of tadalafil's daily therapeutic use in relieving pulmonary arterial hypertension.
Betamethasone is a steroid medication.It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis andsystemic lupus erythematosus, skin diseases such as dermatitis andpsoriasis, allergic conditions such as asthma and angioedema, preterm labor to speed the development of the baby's lungs, Crohn's disease, cancers such as leukemia, and along with fludrocortisone foradrenocortical insufficiency, among others.It can be taken by mouth,injected into a muscle, or applied as a cream.When given by injection, anti-inflammatory effects begin in around two hours and last for seven days.
Betamethasone was approved for medical use in the United States in 1961.The cream is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication.In the United States the pills and injectable solution are expensive while the cream is not.
Aplication:
1. Betamethasone is a corticosteroid used as a topical cream to relieve skin irritation, such as itching and flaking from eczema. It is used as a treatment for local psoriasis, as betamethasone dipropionate and salicylic acid, or as the combination betamethasone/calcipotriol. Betamethasone sodium phosphate is used orally and via injection with the same indications as other steroids.
2. Betamethasone is also used prior to delivery of a preterm baby to help prepare the lung for breathing
Tadalafil's pharmacologic distinction is its longer half-life (17.50 hours) resulting in longer duration of action, and so partly responsible for "The Weekend Pill" sobriquet. Furthermore, the longer half-life is the basis for current investigation of tadalafil's daily therapeutic use in relieving pulmonary arterial hypertension.
Betamethasone is a steroid medication.It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis andsystemic lupus erythematosus, skin diseases such as dermatitis andpsoriasis, allergic conditions such as asthma and angioedema, preterm labor to speed the development of the baby's lungs, Crohn's disease, cancers such as leukemia, and along with fludrocortisone foradrenocortical insufficiency, among others.It can be taken by mouth,injected into a muscle, or applied as a cream.When given by injection, anti-inflammatory effects begin in around two hours and last for seven days.
Betamethasone was approved for medical use in the United States in 1961.The cream is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication.In the United States the pills and injectable solution are expensive while the cream is not.
Aplication:
1. Betamethasone is a corticosteroid used as a topical cream to relieve skin irritation, such as itching and flaking from eczema. It is used as a treatment for local psoriasis, as betamethasone dipropionate and salicylic acid, or as the combination betamethasone/calcipotriol. Betamethasone sodium phosphate is used orally and via injection with the same indications as other steroids.
2. Betamethasone is also used prior to delivery of a preterm baby to help prepare the lung for breathing
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Tadalafil Powder for Sex Enhancement
Model NO.: CAS No.: 171596-29-5
Product Name:buyaas Tadalafil powder
CAS: 171596-29-5
Appearance: White Powder
Function: Men Sex Enhance and Time Extension
Trademark: Huao
Transport Package: Foil Bags
Specification: IOS
HS Code: 3004201911
Effective Tadalafil Powder for Men Sex Enhancement CAS 171596-29-5
Tadalafil is a kind of Male sex hormone product in market , men like it very much . It was oral pills /caps for 10mg , and lasting 72 hours effect ...
Product name: Tadalafil
Key words: Tadalafil , anabolic, bodybuilding, steroid powder
Chemical Formula: C22H19N3O4
Molecular Weight: 389.341
CAS No: 171596-29-5
Packing: Foil bag
Quality standard: USP31/BP2005
White Crystalline Powder
Storage: Shading, Confined Preservation
Usage: Can be used as pharmaceutical material. Its main function is to promote metabolism.
Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.
Delivery: Express courier.
Application:
(tadalafil) relaxes muscles found in the walls of blood vessels and increases blood flow to particular areas of the body.its used to treat erectile dysfunction (impotence) and symptoms of benign prostatic hypertrophy (enlarged prostate).We also call it 36 hours . It could work fast within 30 minutes for men .Also it can last longer, approximately 36 hours ,even 72 hours .
it takes PRN, a tablet may help some men get ready for sexual activity within 30 minutes, which means you will work 36 hours. This means that you and your spouse have plenty of time to taste a relaxing dinner date, a weekend holiday or anniversary celebration, but there is plenty of time to choose if your time is right.
Product Name:buyaas Tadalafil powder
CAS: 171596-29-5
Appearance: White Powder
Function: Men Sex Enhance and Time Extension
Trademark: Huao
Transport Package: Foil Bags
Specification: IOS
HS Code: 3004201911
Effective Tadalafil Powder for Men Sex Enhancement CAS 171596-29-5
Tadalafil is a kind of Male sex hormone product in market , men like it very much . It was oral pills /caps for 10mg , and lasting 72 hours effect ...
Product name: Tadalafil
Key words: Tadalafil , anabolic, bodybuilding, steroid powder
Chemical Formula: C22H19N3O4
Molecular Weight: 389.341
CAS No: 171596-29-5
Packing: Foil bag
Quality standard: USP31/BP2005
White Crystalline Powder
Storage: Shading, Confined Preservation
Usage: Can be used as pharmaceutical material. Its main function is to promote metabolism.
Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.
Delivery: Express courier.
Application:
(tadalafil) relaxes muscles found in the walls of blood vessels and increases blood flow to particular areas of the body.its used to treat erectile dysfunction (impotence) and symptoms of benign prostatic hypertrophy (enlarged prostate).We also call it 36 hours . It could work fast within 30 minutes for men .Also it can last longer, approximately 36 hours ,even 72 hours .
it takes PRN, a tablet may help some men get ready for sexual activity within 30 minutes, which means you will work 36 hours. This means that you and your spouse have plenty of time to taste a relaxing dinner date, a weekend holiday or anniversary celebration, but there is plenty of time to choose if your time is right.
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Carvedilol "effective and safe" in severe chronic heart failure
Carvedilol is effective, safe and well tolerated in patients with severe
chronic heart failure, according to the results of a recent
multinational trial. wisepoqder Carvedilol
The COPERNICUS (carvediol prospective randomised cumulative survival) trial was stopped earlier this year, 12 months ahead of schedule, because of the significant survival benefit seen with carvedilol. All trial patients were offered treatment with carvedilol.
countries enrolled in the study randomly received, as well as standard heart failure treatment, either placebo or carvedilol at a starting dose of 3.125mg twice daily, titrated each week to a dose of 6.25mg, 12.5mg and 25mg twice daily.
Data revealed at the American Heart Association’s conference showed that carvedilol reduced the risk of mortality (all cause) or hospitalisation of patients with severe chronic heart failure by nearly a third (31 per cent). Fewer adverse events and lower withdrawal rates were found with carvedilol compared with placebo.
A previous study of carvedilol, the Carvedilol US Trial Programme, showed a 65 per cent reduction in mortality with carvedilol in patients with mild to moderate heart failure.
In a press release, Roche Pharmaceuticals said that carvedilol was not licensed for treatment of severe heart failure in the UK and that a licence application would be made shortly.
The COPERNICUS (carvediol prospective randomised cumulative survival) trial was stopped earlier this year, 12 months ahead of schedule, because of the significant survival benefit seen with carvedilol. All trial patients were offered treatment with carvedilol.
countries enrolled in the study randomly received, as well as standard heart failure treatment, either placebo or carvedilol at a starting dose of 3.125mg twice daily, titrated each week to a dose of 6.25mg, 12.5mg and 25mg twice daily.
Data revealed at the American Heart Association’s conference showed that carvedilol reduced the risk of mortality (all cause) or hospitalisation of patients with severe chronic heart failure by nearly a third (31 per cent). Fewer adverse events and lower withdrawal rates were found with carvedilol compared with placebo.
A previous study of carvedilol, the Carvedilol US Trial Programme, showed a 65 per cent reduction in mortality with carvedilol in patients with mild to moderate heart failure.
In a press release, Roche Pharmaceuticals said that carvedilol was not licensed for treatment of severe heart failure in the UK and that a licence application would be made shortly.
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Carvedilol with breast cancer treatment reduces echocardiographic findings
Patients with nonmetastatic HER-2 positive breast cancer and weak
markers of HF treated with trastuzumab had reductions in systolic and
diastolic echocardiographic findings when concomitantly treated with
carvedilol, according to findings presented at EuroEcho-Imaging.wisepoqder Carvedilol powder
Maryam Moshkani Farahani, MD, associate professor at Baqiyatallah University of Medical Sciences in Tehran, Iran, and colleagues analyzed data from 71 patients with nonmetastatic HER-2 positive breast cancer who were eligible for treatment with trastuzumab (Herceptin, Genentech). Patients were either assigned carvedilol with trastuzumab (n = 36) or trastuzumab alone (n = 35). Those who were assigned carvedilol received a standard dosage of 6.25 mg twice per day, which was then up-titrated to the maximally tolerated dose.
Left ventricular systolic and diastolic function were evaluated with speckle-tracking echocardiography at baseline and every 3 months.
During follow-up, mean LV ejection fraction did not differ between both groups (P = .61). Patients assigned trastuzumab alone had reductions in strain rate of LV systolic function (P = .004) and global longitudinal strain of LV (P = 0). Those assigned prophylactic carvedilol had preserved LV strain rate of early (P = 0) and late diastolic function (P = .005).
"Heart damage is a major side effect of the breast cancer drug trastuzumab and may force patients to stop treatment,†Moshkani Farahani said in a press release. "Our study suggests that patients who take the beta-blocker carvedilol together with trastuzumab have less heart damage than those who take trastuzumab alone.â€
Zydus Pharmaceuticals USA Inc. is recalling 7668 bottles of carvedilol tablets, 3.125 mg, after a customer found a fragmented tablet of another drug product in a bottle. The recall was announced in the May 1, 2019, US Food and Drug Administration (FDA) Enforcement Report.
The recall is for 500-count bottles from lot Z803518 (Exp. 8/20). Bottles from the affected lot were manufactured by Cadila Healthcare Ltd. and distributed throughout the United States by Zydus Pharmaceuticals.
Zydus Pharmaceuticals voluntarily issued the recall April 22, 2019. On April 25, 2019, the FDA designated the recall Class III, suggesting use of the affected product is unlikely to cause adverse health consequences.Carvedilol is a prescription beta-blocker used to treat heart failure and hypertension.
Maryam Moshkani Farahani, MD, associate professor at Baqiyatallah University of Medical Sciences in Tehran, Iran, and colleagues analyzed data from 71 patients with nonmetastatic HER-2 positive breast cancer who were eligible for treatment with trastuzumab (Herceptin, Genentech). Patients were either assigned carvedilol with trastuzumab (n = 36) or trastuzumab alone (n = 35). Those who were assigned carvedilol received a standard dosage of 6.25 mg twice per day, which was then up-titrated to the maximally tolerated dose.
Left ventricular systolic and diastolic function were evaluated with speckle-tracking echocardiography at baseline and every 3 months.
During follow-up, mean LV ejection fraction did not differ between both groups (P = .61). Patients assigned trastuzumab alone had reductions in strain rate of LV systolic function (P = .004) and global longitudinal strain of LV (P = 0). Those assigned prophylactic carvedilol had preserved LV strain rate of early (P = 0) and late diastolic function (P = .005).
"Heart damage is a major side effect of the breast cancer drug trastuzumab and may force patients to stop treatment,†Moshkani Farahani said in a press release. "Our study suggests that patients who take the beta-blocker carvedilol together with trastuzumab have less heart damage than those who take trastuzumab alone.â€
Zydus Pharmaceuticals USA Inc. is recalling 7668 bottles of carvedilol tablets, 3.125 mg, after a customer found a fragmented tablet of another drug product in a bottle. The recall was announced in the May 1, 2019, US Food and Drug Administration (FDA) Enforcement Report.
The recall is for 500-count bottles from lot Z803518 (Exp. 8/20). Bottles from the affected lot were manufactured by Cadila Healthcare Ltd. and distributed throughout the United States by Zydus Pharmaceuticals.
Zydus Pharmaceuticals voluntarily issued the recall April 22, 2019. On April 25, 2019, the FDA designated the recall Class III, suggesting use of the affected product is unlikely to cause adverse health consequences.Carvedilol is a prescription beta-blocker used to treat heart failure and hypertension.
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The Marfan Foundation Statement on Celiprolol
On June 25, 2019, the FDA announced that it has rejected Acer
Therapeutics’ application for exclusive use of the third generation beta
blocker celiprolol in the US for the treatment of people with vascular
Ehlers-Danlos syndrome (vEDS). This is a rare (about 1/50,000 in the US)
genetic condition that results from mutations in one copy of the COL3A1
gene (which encodes type III collagen) and is complicated by arterial
aneurysm, dissection, and rupture which can lead to premature death.wisepoqder Celiprolol powder
The Marfan Foundation, as well as representatives of its Professional Advisory Board, have reviewed the underlying studies of the drug and agree that celiprolol does not warrant designation as a sole approved drug for the treatment of people with vEDS (see background below). The Foundation recommends that registries of affected individuals with COL3A1 mutations be assembled quickly to facilitate informative clinical trials.
Patients should be aware that there are similar third generation beta-blockers, such as carvedilol, nebivolol, and labetalol, available in the US that are being prescribed off-label for this condition. Both carvedilol and labetalol are generic; therefore, they are very low in cost, and nebivolol will soon come off patent. However, there are no trials or long-term studies utilizing these drugs investigating protective effects in this population.
We suggest that optimal future trial design require molecular confirmation of diagnosis and take into account the type of mutation in a given patient as well as prior medical and surgical history, including vascular events and interventions. The outcomes need to be rigorously defined and ascertained by individuals who are unaware of treatment status in order to avoid bias. The assignment of an individual to the celiprolol or control (no or alternative treatment) group needs to occur at random and be maintained throughout the study.
This proposed prospective, randomized, placebo-controlled, double-blinded, and intention to treat study design is standard in the field and is the most powerful and definitive way to assess for benefit or absence of benefit for celiprolol in vEDS. It is also essential that the study be of sufficient size to reach robust conclusions – including both the number of individuals treated with celiprolol and those receiving placebo or alternative therapy. Alternative medications for testing might include other beta-blockers that are currently available in the US and are inexpensive or other medications that have demonstrated protective effects in animal models. The costs for the trial will be significant, given the nature of surveillance that will probably be needed, and support from multiple sources will have to be obtained.
The Marfan Foundation is eager to assist in protocol design, generation of funds, patient recruitment, and education of both patients and their healthcare providers, as it did with the Pediatric Heart Network Study of the angiotensin-receptor blocker losartan in Marfan syndrome.
The Marfan Foundation, as well as representatives of its Professional Advisory Board, have reviewed the underlying studies of the drug and agree that celiprolol does not warrant designation as a sole approved drug for the treatment of people with vEDS (see background below). The Foundation recommends that registries of affected individuals with COL3A1 mutations be assembled quickly to facilitate informative clinical trials.
Patients should be aware that there are similar third generation beta-blockers, such as carvedilol, nebivolol, and labetalol, available in the US that are being prescribed off-label for this condition. Both carvedilol and labetalol are generic; therefore, they are very low in cost, and nebivolol will soon come off patent. However, there are no trials or long-term studies utilizing these drugs investigating protective effects in this population.
We suggest that optimal future trial design require molecular confirmation of diagnosis and take into account the type of mutation in a given patient as well as prior medical and surgical history, including vascular events and interventions. The outcomes need to be rigorously defined and ascertained by individuals who are unaware of treatment status in order to avoid bias. The assignment of an individual to the celiprolol or control (no or alternative treatment) group needs to occur at random and be maintained throughout the study.
This proposed prospective, randomized, placebo-controlled, double-blinded, and intention to treat study design is standard in the field and is the most powerful and definitive way to assess for benefit or absence of benefit for celiprolol in vEDS. It is also essential that the study be of sufficient size to reach robust conclusions – including both the number of individuals treated with celiprolol and those receiving placebo or alternative therapy. Alternative medications for testing might include other beta-blockers that are currently available in the US and are inexpensive or other medications that have demonstrated protective effects in animal models. The costs for the trial will be significant, given the nature of surveillance that will probably be needed, and support from multiple sources will have to be obtained.
The Marfan Foundation is eager to assist in protocol design, generation of funds, patient recruitment, and education of both patients and their healthcare providers, as it did with the Pediatric Heart Network Study of the angiotensin-receptor blocker losartan in Marfan syndrome.
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CMS 121 FUNDAMENTALS OF FILMMAKING
This introductory course is designed to acquaint students with the basic
elements of film production. Students are taught the aesthetics and
techniques required for producing a short narrative film. They are also
introduced to techniques in producing, writing, cinematography,
directing, and editing. Students are required to write, produce, and
direct a short film. Note: Students are required to share in the
expenses involved in their productions.wisepoqder CMS121
Course Goals: Upon successful completion of this course, students should be able to do the following:
develop a storyboard and script for a short film from an original idea;
utilize cinematographic techniques to convey meaning and create visual interest in a short film;
plan and implement a film shoot with a variety of crew roles; and
edit filmed scenes into a short narrative or experimental film.
Course Goals: Upon successful completion of this course, students should be able to do the following:
develop a storyboard and script for a short film from an original idea;
utilize cinematographic techniques to convey meaning and create visual interest in a short film;
plan and implement a film shoot with a variety of crew roles; and
edit filmed scenes into a short narrative or experimental film.
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Assessing J147 for Alzheimer's in Healthy Volunteers
This Phase I clinical study will assess the safety and pharmacokinetics
of the experimental drug J147 in healthy adults. Researchers are
investigating the drug as a potential treatment for Alzheimer's disease.wisepoqder J147 powder
Exclusion Criteria
History or evidence of heart, endocrine, blood, immune, gastrointestinal, genital, urinary, or other body system disease
History or evidence of disease or dysfunction in neurological or psychiatric system that is likely to affect study results
Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs
Any concurrent disease or condition that would make the participant unsuitable for study participation
Positive for hepatitis B surface antigen, hepatitis C antibody, or HIV antibodies
Positive test for ethanol (alcohol) or cotinine (tobacco) at screening or admission
Positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at screening or admission
Is unwilling to avoid consumption of grapefruit, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days of taking the study drug
History of alcohol and/or illicit drug abuse in past year or is unwilling to avoid use of alcohol or alcohol-containing foods, medications, or beverages within 48 hours of admission until discharge from the clinical unit
Has donated blood or blood products within 30 days of first dosing
Requires treatment with any prescription drugs or over-the-counter medications, including vitamins (large doses), dietary supplements, or herbal medications, within 14 days of study medication (acetaminophen 1,000 mg per day and recommended daily doses of vitamins are permitted)
Has received any known liver or kidney clearance altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, or St. John's wort) within 30 days of study start
Has used an investigational drug within 30 days of screening
Hypersensitivity or allergies to J147, any of its components, or any drug within the same class
Significant abnormal vital signs on physical exam or laboratory results
Is considering or has scheduled any surgical procedure during study participation
Requires a special diet or has a significant food allergy or intolerance (vegetarian diet may be permitted)
Currently enrolled in another clinical study
Evidence of cognitive decline that is greater than expected for participant's age or changes in level of independence in everyday life
Detailed Description
J147 is a synthetic derivative of curcumin, a component of the curry spice turmeric. In this study participants will be randomly assigned to take either the study drug or a placebo in an escalating dose. Doses will first be given to younger participants after an 8-hour fast. Older participants will then receive doses that have been found to be safe in younger participants.
Exclusion Criteria
History or evidence of heart, endocrine, blood, immune, gastrointestinal, genital, urinary, or other body system disease
History or evidence of disease or dysfunction in neurological or psychiatric system that is likely to affect study results
Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs
Any concurrent disease or condition that would make the participant unsuitable for study participation
Positive for hepatitis B surface antigen, hepatitis C antibody, or HIV antibodies
Positive test for ethanol (alcohol) or cotinine (tobacco) at screening or admission
Positive urine drug test (e.g., cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids) at screening or admission
Is unwilling to avoid consumption of grapefruit, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days of taking the study drug
History of alcohol and/or illicit drug abuse in past year or is unwilling to avoid use of alcohol or alcohol-containing foods, medications, or beverages within 48 hours of admission until discharge from the clinical unit
Has donated blood or blood products within 30 days of first dosing
Requires treatment with any prescription drugs or over-the-counter medications, including vitamins (large doses), dietary supplements, or herbal medications, within 14 days of study medication (acetaminophen 1,000 mg per day and recommended daily doses of vitamins are permitted)
Has received any known liver or kidney clearance altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, or St. John's wort) within 30 days of study start
Has used an investigational drug within 30 days of screening
Hypersensitivity or allergies to J147, any of its components, or any drug within the same class
Significant abnormal vital signs on physical exam or laboratory results
Is considering or has scheduled any surgical procedure during study participation
Requires a special diet or has a significant food allergy or intolerance (vegetarian diet may be permitted)
Currently enrolled in another clinical study
Evidence of cognitive decline that is greater than expected for participant's age or changes in level of independence in everyday life
Detailed Description
J147 is a synthetic derivative of curcumin, a component of the curry spice turmeric. In this study participants will be randomly assigned to take either the study drug or a placebo in an escalating dose. Doses will first be given to younger participants after an 8-hour fast. Older participants will then receive doses that have been found to be safe in younger participants.
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Alpha-Lipoic Acid: Weight Loss, Other Benefits and Side Effects
Alpha-lipoic acid has gained a lot of attention in recent years.It’s an
organic compound that acts as a powerful antioxidant in the body.Your
body produces alpha-lipoic acid naturally, but it’s also found in a
variety of foods and as a dietary supplement.Research suggests that it
may play a role in weight loss, diabetes, and other health conditions.
However, many people wonder whether it’s effective.This article reviews alpha-lipoic acid, its benefits, side effects, and recommended dosage.wisepoqder Alpha-lipoic Acid
What is alpha-lipoic acid?
Alpha-lipoic acid is an organic compound found in all human cells.It’s made inside the mitochondrion — also known as the powerhouse of cells — where it helps enzymes turn nutrients into energy (1).What’s more, it has powerful antioxidant properties.
Alpha-lipoic acid is both water- and fat-soluble, which allows it to work in every cell or tissue in the body. Meanwhile, most other antioxidants are either water- or fat-soluble (2).For instance, vitamin C is only water-soluble, while vitamin E is only fat-soluble.
The antioxidant properties of alpha-lipoic acid have been linked to several benefits, including lower blood sugar levels, reduced inflammation, slowed skin aging, and improved nerve function.Humans only produce alpha-lipoic acid in small amounts. That’s why many turn to certain foods or supplements to optimize their intake.
Animal products like red meat and organ meats are great sources of alpha-lipoic acid, but plant foods like broccoli, tomatoes, spinach, and Brussels sprouts also contain it.That said, supplements can pack up to 1,000 times more alpha-lipoic acid than food sources (3).
Alpha-lipoic acid and weight loss
Research has shown that alpha-lipoic acid may affect weight loss in several ways.Animal studies indicate that it can reduce the activity of the enzyme AMP-activated protein kinase (AMPK), which is located in your brain’s hypothalamus (4, 5).
When AMPK is more active, it may increase feelings of hunger.On the other hand, suppressing AMPK activity may increase the number of calories your body burns at rest. Thus, animals who took alpha-lipoic acid burned more calories (6, 7).
However, human studies show that alpha-lipoic acid only slightly impacts weight loss.An analysis of 12 studies discovered that people who took an alpha-lipoic acid supplement lost an average of 1.52 pounds (0.69 kg) more than those taking a placebo over an average of 14 weeks (
.In the
same analysis, alpha-lipoic acid did not significantly affect waist
circumference.
Another analysis of 12 studies found that people who took alpha-lipoic acid lost an average of 2.8 pounds (1.27 kg) more than those taking a placebo over an average of 23 weeks (9).In short, it seems that alpha-lipoic acid has just a slight effect on weight loss in humans.
However, many people wonder whether it’s effective.This article reviews alpha-lipoic acid, its benefits, side effects, and recommended dosage.wisepoqder Alpha-lipoic Acid
What is alpha-lipoic acid?
Alpha-lipoic acid is an organic compound found in all human cells.It’s made inside the mitochondrion — also known as the powerhouse of cells — where it helps enzymes turn nutrients into energy (1).What’s more, it has powerful antioxidant properties.
Alpha-lipoic acid is both water- and fat-soluble, which allows it to work in every cell or tissue in the body. Meanwhile, most other antioxidants are either water- or fat-soluble (2).For instance, vitamin C is only water-soluble, while vitamin E is only fat-soluble.
The antioxidant properties of alpha-lipoic acid have been linked to several benefits, including lower blood sugar levels, reduced inflammation, slowed skin aging, and improved nerve function.Humans only produce alpha-lipoic acid in small amounts. That’s why many turn to certain foods or supplements to optimize their intake.
Animal products like red meat and organ meats are great sources of alpha-lipoic acid, but plant foods like broccoli, tomatoes, spinach, and Brussels sprouts also contain it.That said, supplements can pack up to 1,000 times more alpha-lipoic acid than food sources (3).
Alpha-lipoic acid and weight loss
Research has shown that alpha-lipoic acid may affect weight loss in several ways.Animal studies indicate that it can reduce the activity of the enzyme AMP-activated protein kinase (AMPK), which is located in your brain’s hypothalamus (4, 5).
When AMPK is more active, it may increase feelings of hunger.On the other hand, suppressing AMPK activity may increase the number of calories your body burns at rest. Thus, animals who took alpha-lipoic acid burned more calories (6, 7).
However, human studies show that alpha-lipoic acid only slightly impacts weight loss.An analysis of 12 studies discovered that people who took an alpha-lipoic acid supplement lost an average of 1.52 pounds (0.69 kg) more than those taking a placebo over an average of 14 weeks (
.In the
same analysis, alpha-lipoic acid did not significantly affect waist
circumference.Another analysis of 12 studies found that people who took alpha-lipoic acid lost an average of 2.8 pounds (1.27 kg) more than those taking a placebo over an average of 23 weeks (9).In short, it seems that alpha-lipoic acid has just a slight effect on weight loss in humans.
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Alpha Lipoic Acid (ALA)
Alpha-lipoic acid or ALA is a naturally occurring compound that's made
in the body. It serves vital functions at the cellular level, such as
energy production. As long as you're healthy, the body can produce all
the ALA it needs for these purposes. Despite that fact, there has been a
lot of recent interest in using ALA supplements. Advocates of ALA make
claims that range from beneficial effects for treating conditions such
as diabetes and HIV to enhancing weight loss.wisepoqder Alpha-lipoic Acid powder
Research on the effects of ALA supplementation is sparse. What there is, though, does suggest some possible benefits. Here is what's known about the potential health benefits of using alpha-lipoic acid supplements.
ALA is an antioxidant. Antioxidants protect against damage to the body's cells.
There are food sources of ALA such as yeast, organ meats like liver and heart, spinach, broccoli, and potatoes. However, ALA from food does not appear to produce a noticeable increase in the level of free ALA in the body.Some people take ALA supplements with the intent to improve a variety of health conditions. Scientific evidence for the health benefit of supplemental ALA has been inconclusive.
Studies show that about 30% to 40% of the oral dose of an ALA supplement is absorbed. ALA may be better absorbed if it is taken on an empty stomach.
While studies are still sparse, there is some evidence that ALA may have at least two positive benefits for individuals with type 2 diabetes. A few studies have suggested that alpha-lipoic acid supplements may enhance the body's ability to use its own insulin to lower blood sugar in people with type 2 diabetes. ALA may help reduce the symptoms of peripheral neuropathy -- nerve damage that can be caused by diabetes.
In Europe, ALA has been used for years to provide relief from the pain, burning, tingling, and numbing caused by diabetic neuropathy. In particular, one large study strongly suggested that large intravenous doses of ALA were effective at relieving symptoms. But the evidence for oral doses is not as strong. More research is needed to establish the effectiveness of oral ALA supplements for diabetic neuropathy.
Research on the effects of ALA supplementation is sparse. What there is, though, does suggest some possible benefits. Here is what's known about the potential health benefits of using alpha-lipoic acid supplements.
ALA is an antioxidant. Antioxidants protect against damage to the body's cells.
There are food sources of ALA such as yeast, organ meats like liver and heart, spinach, broccoli, and potatoes. However, ALA from food does not appear to produce a noticeable increase in the level of free ALA in the body.Some people take ALA supplements with the intent to improve a variety of health conditions. Scientific evidence for the health benefit of supplemental ALA has been inconclusive.
Studies show that about 30% to 40% of the oral dose of an ALA supplement is absorbed. ALA may be better absorbed if it is taken on an empty stomach.
While studies are still sparse, there is some evidence that ALA may have at least two positive benefits for individuals with type 2 diabetes. A few studies have suggested that alpha-lipoic acid supplements may enhance the body's ability to use its own insulin to lower blood sugar in people with type 2 diabetes. ALA may help reduce the symptoms of peripheral neuropathy -- nerve damage that can be caused by diabetes.
In Europe, ALA has been used for years to provide relief from the pain, burning, tingling, and numbing caused by diabetic neuropathy. In particular, one large study strongly suggested that large intravenous doses of ALA were effective at relieving symptoms. But the evidence for oral doses is not as strong. More research is needed to establish the effectiveness of oral ALA supplements for diabetic neuropathy.
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04:40 PM
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5 Ways to Use L-arginine for Weight Loss
L-arginine, an amino acid, is found in foods like dairy products and
meats. It helps in bodybuilding, muscle development, and improved
performance.
These benefits have been researched with most conclusions being made after extensive studies.One study showed that L-arginine improves DNA synthesis and mitochondrial bioenergetics, which may also be responsible for the beneficial effects of Arg on intestinal mucosal cells.wisepoqder L(+)-Arginine
L-arginine is produced by the body in adequate amounts to elevate the action of a nitric acid in the body. It also has biochemical components that enhance the metabolism of fats.It is mostly given to people dealing with obesity to help burn the fat and enhance the formation of muscle mass. Supplementing with l-arginine allows your body to use accumulated fats as a source of energy.
The accumulated fat is burnt to produce energy and to aid in muscle mass formation and development. L-arginine thus boosts your body metabolism as well as forms building blocks for muscle formation.As a result, you lose fat mass but retain your muscle mass.
To test the efficacy of l-arginine on weight loss, a research study was conducted. L-arginine supplements were given to obese males who had type 2 diabetes to see if it would help in weight loss.
The study had more than 300 subjects who were subjected to the l-arginine and placebo groups.They consumed 1000kcal per day and exercised 90 minutes every day for five days in a week. They also took 8.3g of l-arginine per day.
The results from the 21-day study showed that l-arginine increases weight loss. People who got l-arginine showed that 100 percent of the weight loss was all fat compared to those on placebo who lost up to 40 percent muscle mass.
Larger doses of l-arginine for weight loss allow for faster fat burning, which is needed in the development of a leaner body:
The upper recommended l-arginine amount per serving is 5 to 10 grams. You should start with a lower serving and increase the dosage as you continue to use the supplement. It stimulates more body fat burning and formation of muscle, thus making it ideal for people looking to lose weight.
This supplement is highly effective in the treatment of obesity. However, excessive use can lead to harmful side effects.Amino acids are known to aid in bodybuilding. For instance, l-arginine minimizes the action of the adipose tissue, which is the belly fat. Obesity is mainly characterized by stores of belly fat. The more a person accumulates the belly fat, the higher the risk of developing cardiovascular diseases.
Stimulates production of HGH
L-arginine also increases the levels of HGH (Human Growth Hormone) that supports increased metabolism. However, it increases HGH levels when taken in very large amounts. Taking large amounts of the supplement is not advisable, however, because it can cause side effects such as stomach cramps and diarrhea.
Increased energy:
Additionally, l-arginine is an ingredient long used in supplement formulas. It has been used for a wide range of functions including the enhancement of sports performance and boosting cardiovascular health. Since it is a nitrogenous acid, it stimulates the production of a nitric oxide whose making function is to dilate the blood vessels. Increased blood flow through the body increases energy and enhances the overall body performance.
Dilated vessels ease the work of the heart, thus improving your cardiovascular health by lowering your blood pressure. They also transport blood faster to different pressure points, which increases your energy for workouts.
Besides increasing your energy, dilated blood vessels also act as a treatment basis for erectile dysfunction.Some studies have pointed out that it increases semen production, implying that could boost sexual performance. It prevents renal dysfunction in patients with type- 2 diabetes.
These benefits have been researched with most conclusions being made after extensive studies.One study showed that L-arginine improves DNA synthesis and mitochondrial bioenergetics, which may also be responsible for the beneficial effects of Arg on intestinal mucosal cells.wisepoqder L(+)-Arginine
L-arginine is produced by the body in adequate amounts to elevate the action of a nitric acid in the body. It also has biochemical components that enhance the metabolism of fats.It is mostly given to people dealing with obesity to help burn the fat and enhance the formation of muscle mass. Supplementing with l-arginine allows your body to use accumulated fats as a source of energy.
The accumulated fat is burnt to produce energy and to aid in muscle mass formation and development. L-arginine thus boosts your body metabolism as well as forms building blocks for muscle formation.As a result, you lose fat mass but retain your muscle mass.
To test the efficacy of l-arginine on weight loss, a research study was conducted. L-arginine supplements were given to obese males who had type 2 diabetes to see if it would help in weight loss.
The study had more than 300 subjects who were subjected to the l-arginine and placebo groups.They consumed 1000kcal per day and exercised 90 minutes every day for five days in a week. They also took 8.3g of l-arginine per day.
The results from the 21-day study showed that l-arginine increases weight loss. People who got l-arginine showed that 100 percent of the weight loss was all fat compared to those on placebo who lost up to 40 percent muscle mass.
Larger doses of l-arginine for weight loss allow for faster fat burning, which is needed in the development of a leaner body:
The upper recommended l-arginine amount per serving is 5 to 10 grams. You should start with a lower serving and increase the dosage as you continue to use the supplement. It stimulates more body fat burning and formation of muscle, thus making it ideal for people looking to lose weight.
This supplement is highly effective in the treatment of obesity. However, excessive use can lead to harmful side effects.Amino acids are known to aid in bodybuilding. For instance, l-arginine minimizes the action of the adipose tissue, which is the belly fat. Obesity is mainly characterized by stores of belly fat. The more a person accumulates the belly fat, the higher the risk of developing cardiovascular diseases.
Stimulates production of HGH
L-arginine also increases the levels of HGH (Human Growth Hormone) that supports increased metabolism. However, it increases HGH levels when taken in very large amounts. Taking large amounts of the supplement is not advisable, however, because it can cause side effects such as stomach cramps and diarrhea.
Increased energy:
Additionally, l-arginine is an ingredient long used in supplement formulas. It has been used for a wide range of functions including the enhancement of sports performance and boosting cardiovascular health. Since it is a nitrogenous acid, it stimulates the production of a nitric oxide whose making function is to dilate the blood vessels. Increased blood flow through the body increases energy and enhances the overall body performance.
Dilated vessels ease the work of the heart, thus improving your cardiovascular health by lowering your blood pressure. They also transport blood faster to different pressure points, which increases your energy for workouts.
Besides increasing your energy, dilated blood vessels also act as a treatment basis for erectile dysfunction.Some studies have pointed out that it increases semen production, implying that could boost sexual performance. It prevents renal dysfunction in patients with type- 2 diabetes.
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L-Arginine Assay Kit (Colorimetric)
L-Arginine (Arg) is a proteogenic, semi-essential amino acid: healthy
humans can synthesize L-Arginine using L-Glutamine as a building block;
however, premature infants are unable to produce Arg and additional
supplementation is required for proper growth and development. Arginine
plays pivotal roles in biochemical pathways such as the urea cycle and
the biosynthesis of nitric oxide. Arginine and Ammonia concentrations
are elevated in patients having a mutation in their ARG1 genes. The
mutation causes lower arginase activities – a condition that is known as
Argininemia. Arginine has also been advertised as a supplement due to
its role in the synthesis of nitric oxide, which helps in vasodilation
processes.wisepoqder L(+)-Arginine powder
BioVision's L-Arginine Assay Kit provides a quick, specific, and easy method for the measurement of total L-arginine concentrations in a wide variety of samples. In this enzyme-based assay, L-arginine is converted into a series of intermediates, which will further react with a probe producing a stable colorimetric signal (OD: 450 nm). The kit is simple to use, sensitive and high-throughput adaptable and can detect as low as 1 nmol/well of L-arginine in biological samples.
BioVision's L-Arginine Assay Kit provides a quick, specific, and easy method for the measurement of total L-arginine concentrations in a wide variety of samples. In this enzyme-based assay, L-arginine is converted into a series of intermediates, which will further react with a probe producing a stable colorimetric signal (OD: 450 nm). The kit is simple to use, sensitive and high-throughput adaptable and can detect as low as 1 nmol/well of L-arginine in biological samples.
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Arginine: Heart Benefits and Side Effects
There are plenty of powerful new drugs to help prevent and treat chronic
health problems. But we also know that certain nutrients may help, as
well. Take arginine, for example. Arginine has gotten lots of attention
lately for its potential heart benefits. That's important because,
today, about 85.6 million Americans have some form of cardiovascular
disease.wisepoqder Antiaging Powder
Deficiencies of arginine are rare. It's abundant in many different types of foods, and your body can also make it. Arginine-rich foods include red meat, fish, poultry, wheat germ, grains, nuts and seeds, and dairy products. But what does arginine do for the heart, and are there potential side effects?As a natural dietary supplement, arginine has garnered particular attention for its possible heart benefits.
What Are Arginine's Heart Benefits?
In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation.
Some evidence shows that arginine may help improve blood flow in the arteries of the heart. That may improve symptoms of clogged arteries, chest pain or angina, and coronary artery disease. However, there currently is no data on how the long-term use of arginine affects cholesterol or heart health.Since arginine may help arteries relax and improve blood flow, it may also help with erectile dysfunction.
There are other potential health benefits with arginine, such as possible reduction of blood pressure in some people and improved walking distance in patients with intermittent leg cramping and weakness known as intermittent claudication. However, the scientific studies are not conclusive enough for experts to make any firm recommendations.
Not all studies on arginine have been positive. A 2006 study showed that arginine was not helpful -- and may have been harmful -- for treating heart attacks in combination with standard treatment.
Deficiencies of arginine are rare. It's abundant in many different types of foods, and your body can also make it. Arginine-rich foods include red meat, fish, poultry, wheat germ, grains, nuts and seeds, and dairy products. But what does arginine do for the heart, and are there potential side effects?As a natural dietary supplement, arginine has garnered particular attention for its possible heart benefits.
What Are Arginine's Heart Benefits?
In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation.
Some evidence shows that arginine may help improve blood flow in the arteries of the heart. That may improve symptoms of clogged arteries, chest pain or angina, and coronary artery disease. However, there currently is no data on how the long-term use of arginine affects cholesterol or heart health.Since arginine may help arteries relax and improve blood flow, it may also help with erectile dysfunction.
There are other potential health benefits with arginine, such as possible reduction of blood pressure in some people and improved walking distance in patients with intermittent leg cramping and weakness known as intermittent claudication. However, the scientific studies are not conclusive enough for experts to make any firm recommendations.
Not all studies on arginine have been positive. A 2006 study showed that arginine was not helpful -- and may have been harmful -- for treating heart attacks in combination with standard treatment.
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First-in-human trial of senolytic drugs encouraging
Senolytics target cellular senescence, a process in which damaged cells,
rather than dying, persist and become toxic to cells around them.
Cellular senescence has been shown to drive multiple age-related
diseases, including idiopathic pulmonary fibrosis (IPF), a chronic,
irreversible and progressive disease that results in scarring of the
lungs. In animal studies, run by Mayo Clinic collaborators James
Kirkland, M.D., Ph.D.; Nathan LeBrasseur, Ph.D., M.S., and Tamara
Tchkonia, Ph.D., senolytics selectively cleared these toxic cells in
mice that model IPF.wisepoqder Quercetin
A lethal disease for which there are few options
"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than five years in newly diagnosed adults usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio and founding director of the university's Interstitial Lung Disease Program, one of 60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr. Nambiar is co-first author of the research manuscript and enrolled 12 of the patients at UT Health San Antonio and the South Texas Veterans Health Care System.
Despite the current availability of two U.S. Food and Drug Administration-approved therapies that may slow down disease progression in some IPF patients, the prognosis remains poor and is worse than for many common cancers, Dr. Nambiar said. Lung transplantation may be lifesaving, but often is only an option for younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.
Patients enrolled in Texas, North Carolina
In this first-in-human pilot study, the investigators enrolled 14 older adults diagnosed with stable, primarily mild-to-moderate IPF. Participants were enrolled at both UT Health San Antonio, which served as the primary patient recruitment site, and Wake Forest medical school, which initiated the trial and served as the study coordinating center. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," said Jamie Justice, Ph.D., assistant professor at Wake Forest medical school, co-lead investigator and corresponding study author. "Here, we've therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients. This small study represents a major paradigm shift in treatment strategy."
Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.
The research team measured clinical laboratory chemistries before and after DQ administration, and performed rigorous symptom questionnaires weekly of health, quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function including six-minute walk distance, walking speed, sitting-to-standing repetitions, a frailty index based on clinical laboratory chemistries, and biological assays of senescence-associated proteins secreted by the toxic cells.
A lethal disease for which there are few options
"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than five years in newly diagnosed adults usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio and founding director of the university's Interstitial Lung Disease Program, one of 60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr. Nambiar is co-first author of the research manuscript and enrolled 12 of the patients at UT Health San Antonio and the South Texas Veterans Health Care System.
Despite the current availability of two U.S. Food and Drug Administration-approved therapies that may slow down disease progression in some IPF patients, the prognosis remains poor and is worse than for many common cancers, Dr. Nambiar said. Lung transplantation may be lifesaving, but often is only an option for younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.
Patients enrolled in Texas, North Carolina
In this first-in-human pilot study, the investigators enrolled 14 older adults diagnosed with stable, primarily mild-to-moderate IPF. Participants were enrolled at both UT Health San Antonio, which served as the primary patient recruitment site, and Wake Forest medical school, which initiated the trial and served as the study coordinating center. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," said Jamie Justice, Ph.D., assistant professor at Wake Forest medical school, co-lead investigator and corresponding study author. "Here, we've therapeutically targeted a fundamental biological hallmark of aging that is implicated in IPF, and we show early but promising results for the first time in human patients. This small study represents a major paradigm shift in treatment strategy."
Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.
The research team measured clinical laboratory chemistries before and after DQ administration, and performed rigorous symptom questionnaires weekly of health, quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function including six-minute walk distance, walking speed, sitting-to-standing repetitions, a frailty index based on clinical laboratory chemistries, and biological assays of senescence-associated proteins secreted by the toxic cells.
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Nanoparticles Enhance Quercetin to Selectively Destroy Senescent Cells
Researchers have demonstrated that nanoparticles coated with quercetin
molecules can selectively target and eliminate harmful senescent cells.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
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Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age
NAD+ availability decreases with age and in certain disease conditions.
Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been
shown to enhance NAD+ biosynthesis and ameliorate various pathologies in
mouse disease models. In this study, we conducted a 12-month-long NMN
administration to regular chow-fed wild-type C57BL/6N mice during their
normal aging. Orally administered NMN was quickly utilized to synthesize
NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated
physiological decline in mice. Without any obvious toxicity or
deleterious effects, NMN suppressed age-associated body weight gain,
enhanced energy metabolism, promoted physical activity, improved insulin
sensitivity and plasma lipid profile, and ameliorated eye function and
other pathophysiologies. Consistent with these phenotypes, NMN prevented
age-associated gene expression changes in key metabolic organs and
enhanced mitochondrial oxidative metabolism and mitonuclear protein
imbalance in skeletal muscle. These effects of NMN highlight the
preventive and therapeutic potential of NAD+ intermediates as effective
anti-aging interventions in humans.wisepoqder beta-Nicotinamide mononucleotide powder
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
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Pyrroloquinoline Quinone (PQQ)
Pyrroloquinoline Quinone (PQQ) is a unique micro-nutrient; a
vitamin-like compound found naturally in plant foods and green tea. PQQ
has been shown to provide a wide range of benefits to brain and body
function based upon clinical evaluations. PQQ has been researched and
studied closely for over 30 years.wisepoqder Pyrroloquinoline quinone
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a "fountain of youth†effectâ€. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a "fountain of youth†effectâ€. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
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Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis by Activating
Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in
various foods and mammalian tissues, has received an increasing amount
of attention because of a number of health benefits that can be
attributed to its ability to enhance mitochondrial biogenesis. However,
its underlying molecular mechanism remains incompletely understood. We
have now established that the exposure of mouse NIH/3T3 fibroblasts to a
physiologically relevant concentration of PQQ significantly stimulates
mitochondrial biogenesis.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
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