Italian Hair Loss Lotion To Hit The Market In 2016
- Thread starter paleocapa89
- Start date
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We could have said the same "wow this is IT" stuff about fina and minoxidil when they came out, and look how bust that sh*t is for most people. I hold very little faith in this, and won't be a believer until i see a majority positive response amongst the general consumer population, and not just a 60 person trial.
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- 144
If it truly works I do not particularly mind when it gets released as long as it's in 2018
Most likely to how the Lozione might replace the Big 3 I think
comeback here in 10 hours, by that time we'll know exactly about what we were waiting for.
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- 512
I don't think it is a substitution, in any case, it will be another alternative.
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Switzer
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While we wait, some of you may be interested in reading a paper by Brotzu on treating diabetic microcirculation with a formulation containing PGE1 and l-carnitine. While it says nothing about hair growth, it does discuss the ingredients mechanism of action.
A New Drug for the Treatment of Diabetic Microcirculation: New Formulation of PGE1 α-Cyclodextrin and L. Propionil-Carnitine in Liposomes Covered with Polylysine
Brotzu Giovanni1* and Bajamonte Myrta2
1 Professor Vascular Surgery, Cagliari Medicine University, Italy
2 Senior Clinical Embryologist Director, Palermo Medicine University, Italy
*Corresponding Author: Brotzu Giovanni, Tissue’s Micro Circle Scientific Director IVF Mediterranean Centre, Full Professor Vascular Surgery, Cagliari Medicine University, Italy.
Received: August 07, 2015; Published: September 09, 2015
Abstract
The Prostaglandin E1 and L. Propionil-carnitine are used today for the vascular disease treatment of various origin. The Prostaglandin E1 injected intravenously has a half-life is very short because metabolized predominantly by pulmonary filter and therefore does not arrive in sufficient amount in the capillaries. You have to remember that hyperglycemia impairs endothelial cells especially at the peripheral level, kidney, retina, skin microcirculation and muscle. The association PGE1 and L. Propionil-carnitine, transported by liposomes high adhesiveness not being metabolized in the lungs, is able to perform its function pharmacological on endothelial cells damaged by various diseases, such as diabetes or in TAO, especially in the capillaries where blood flow is slowed down. We intend to study the pharmacological response of our new liposomal formulation of PGE1 more L. Propionil-carnitine on peripheral microcirculation of diabetic patients presenting pathologies. Purchase new Formulation PGE1 e L. Propionil-carnitine produced by a GMP firm.
Introduction
Diabetes is a chronic disease characterized by the presence of high levels of blood glucose (hyperglycemia) and due to an altered amount or insulin function. Insulin is the hormone produced by the pancreas, which allows the glucose entry into cells and its subsequent use as an energy source. When this mechanism is altered, the glucose accumulates in the bloodstream. There are various types: Type 1 diabetes accounts for about 10% of people with diabetes and usually occurs in childhood or adolescence. For this reason, the Type 1 diabetes is classified among the diseases so-called “autoimmune”, that is due to an immune reaction directed against the body itself. Type 2 diabetes is the most common form of diabetes and represents about 90% of cases of this disease. The cause of Type 2 diabetes is unknown but characteristic is the presence in the blood of antibodies directed against antigens present at the level of insulin-producing cells, said ICA, GAD, IA-2, IA-2SS. The cause is still unknown, although it is certain that the pancreas is able to produce insulin, but the cells of the organism cannot then in use. Typically, the disease occurs after 30-40 years and many risk factors have been recognized associate to its onset. These include: the family history of diabetes, lack of exercise, being overweight and belonging to certain ethnic groups.
Type 2 diabetes usually goes undetected for many years because the hyperglycemia develops gradually and is initially not severe enough to give the classic symptoms of diabetes. Usually the diagnosis is done randomly or in conjunction with a situation of physical stress, such as infection or surgery. The risk of developing the disease increases with age, with the presence of obesity and lack of physical activity: this observation allows to predict prevention strategies “primary” that interventions can prevent the onset of the disease and that have their cornerstone in the application of a proper lifestyle, including nutritional and exercise. Gestational diabetes: Gestational diabetes is defined every situation in which a high level of measuring circulating glucose for the first time during pregnancy. This condition occurs in about 4% of pregnancies. The definition is independent of the type of treatment used, it’s just the dietary or the need for insulin and implies a higher frequency of checks for pregnant and the fetus. The symptoms of the onset of the disease depend on the type of diabetes. In the case of Type 1 diabetes usually are witnessing an acute onset, often in connection with a febrile episode, with thirst polydipsia), increased amounts of urine (polyuria), is feeling fatigue (asthenia), weight loss, dry skin, increased frequency of infections.
In Type 2 diabetes, however, the symptoms are more nuanced and usually do not allow a quick diagnosis, so often your blood sugar is high but without clinical signs of Type 1 diabetes. Diabetes can cause acute or chronic complications. Acute complications are more common in Type 1 diabetes and are related to the almost total lack of insulin. In these cases, the patient may experience ketoacidosis coma, due to accumulation of products of altered metabolism, ketones which cause loss of consciousness, dehydration and serious blood disorders. In Type 2 diabetes acute complications are rare, but are very frequent chronic complications that affect different organs and tissues, including the eyes, kidneys, heart, blood vessels and peripheral nerves. The complications of diabetes is Type 1 and 2 are:
1. Diabetic retinopathy: is damage to the small blood vessels that supply the retina with loss of the sight. In addition, people with diabetes are more likely to develop eye diseases such as glaucoma and cataracts.
2. Diabetic nephropathy: it is a gradual reduction of the filter function of the kidney that, if left untreated, can lead to renal insufficiency up to the need for dialysis and/or kidney transplant.
3. Cardiovascular disease: the risk of cardiovascular disease is 2 to 4 times higher in people with diabetes than in the general population resulting in industrialized countries, more than 50% of deaths from diabetes. This leads us to consider the cardiovascular risk in diabetic patients equal to that given to a patient who had a cardiovascular event
4. Diabetic neuropathy: is one of the most frequent complications and according to the World Health Organization is manifested at different levels in 50% of diabetics. It can cause loss of feeling, pain of varying intensity and limb injuries, requiring amputation in severe cases. Can lead to malfunctions of the heart, eyes, stomach and is one of the main causes of male impotence.
5. Diabetic foot: the modifications of the structure of blood vessels and nerves can cause ulceration and problems in the lower limbs, especially the foot, due to loads that. This may necessitate the amputation of limbs and statistically is the leading cause of lower limb amputation for non-traumatic
6. Complications in pregnancy: pregnant women, diabetes can result in adverse consequences on the fetus, congenital malformations with a high birth weight, up to a high risk of perinatal mortality. The high frequency of vascular complications requiring close monitoring of target organs (eyes, kidneys and lower limbs). For this reason, it is necessary for people with diabetes to undergo regular check-ups, even in the absence of symptoms.
Microcirculation refers to the blood circulation in the capillaries and agree that the diameter of these vessels go from 40 to 5 micra. At the beginning of the capillaries from the arterial side there are muscular structures, called pericytes, which regulate the flow while in most peripheral level the capillaries and from the venous side are constituted only by endothelial cells. Microangiopathy is a disease that affects the microcirculation and this being different from organ to organ there are several types of microangiopathy. The diabetes affects the endothelial cells throughout the body causing different diseases.
Microangiopathy is a disease in diabetic patients and it is installed over time and therefore can be considered a chronic disease. At the level of the microcirculation hyperglycemia causes:
1. Increased apoptosis of endothelial cells;
2. The decreased ability of reproduction of endothelial cells;
3. The increase of endothelin which reduces the diameter of the capillaries;
4. Slow blood flow in the capillaries;
The consequence of the above phenomena is primarily tissue oxygenation decrease. The theoretical basis for the use of prostaglandins in Critical Limb Ischemia (CLI) are well known [1]. The Prostaglandin E1 and Prostacyclin expand and improve the local flow. The prostaglandin E1 has an angiogenic and anti-inflammatory effect and improves endothelial function. The PGE1 stimulates endothelial cells VEGF receptors and facilitates the reproduction to maintain sufficient capillarization in the tissue. The problem existing is that Prostaglandin E1 injected intravenously has a half-life very short (less 1 min.) because metabolised predominantly by pulmonary filter and therefore does not arrive in sufficient amount in the capillaries, and the amount injected in increased there are side effects (tachycardia, hypotension, etc.). In fact, the therapeutic administration of PGE1 causes a vasodilatation but also a marked hypotension. Both PGE1 that Iloprost, Prostacyclin analogue, have been evaluated in several clinical trials in patients with CLI. The results of all these studies have failed to demonstrate the true clinical utility of the treatment of arterial disease with prostanoids. Treatment with PGE1 has been approved by the Min of Health, as already mentioned, has never had much success. For that reason have been proposed Prostacyclin analogs that have a half-life greater (Iloprost). But also this search and was performed on patients with systolic pressures at the level of the tibial lower than 50 mmHg and not in patients with microangiopathy and gave results somewhat uncertain [2].
In 1991, our group experienced the treatment of microangiopathy of different origin, IIb and stage III sec. Fontaine (diabetic, from connective tissue, and in Buerger’s disease) with a continuous Iloprost infusion, via elastomeric pump, for a period of 28 days. The results of these studies we did observe that it was possible to obtain a marked improvement of symptoms due to microangiopathy. Infusion therapy with prostanoids was used both before and after surgical revascularization [3]. The goal of therapy was to reduce the phenomena closely related to microangiopathy.
In fact therapy with Iloprost or with PGE1 causes vasodilation, reduces platelet aggregation and restores the functions of endothelial tissue, but is not able to increase the flow in the presence of stenosis or obstruction of macrocirculation. The PGE1 has, as has already been said, a short half-life, but that compared to Iloprost, has the advantage of better reactivate the system functionality endothelial, acting on the VEGF receptor, and at the same time causes a marked vasodilation and if injected directly into the artery in the districts with decreased blood flow causes a marked peripheral vasodilation. But this practice cannot be used for a routine treatment. If injected intravenously its short half-life, lower per minute limits its therapeutic action. By some researchers has been observed that the therapeutic effect improves when PGE1 is associated together with the l-propionyl-carnitine in the treatment of microangiopathies of various origin and in Buerger’s disease to stage II or III. To determine a pharmacological action on the microcirculation, damaged by diabetic pathology, it has been proposed to carry the PGE1 from liposomes that cross the pulmonary filter and have the characteristic of adhering to endothelial cells, especially in sites where there is a microangiopathy and blood flow slows down, and for a low blood pressure and because the endothelial cells are damaged by diabetes [4].
The new formulation was performed at the Department of Chemistry and pharmaceutical technology direct from Prof. Fadda. (See attachment # 1 chemical and physical exam). The liposomes of phosphatidylcholine have the ability to overcome the filter lung to adhere to the endothelial cells of the capillaries species in districts where the blood flow is slowed down and release the drug directly at the level of the peripheral microcirculation.
In the experiments performed in diabetic rats with streptozocin we observed that the administration of liposomes coated with polylysine containing PGE1 more L. Propionil-carnitine determined compared to untreated rats:
1. Decrease endothelial apoptosis in the kidneys in the lungs in the muscle
2. Increase of VEGF
3. Lower water consumption, and better renal function
These observations lead us to propose the use of PGE1 α-cyclodextrin and L. Propionil carnitine transported by liposomes of phosphatidylcholine coated with polylysine in clinical use for the treatment of diabetic foot and microangiopathy in general.
Objectives
The objective of the study is to demonstrate that administration of PGE1 together with L. Propionil-carnitine transported by liposomes is able to determine the healing or at least a net improvement of microangiopathies induced by diabetes. In particular, we wish to observe whether it is possible to obtain a result pharmacological stable over time.
Material and Methods
Because diabetic microangiopathy are chronic diseases is essential to observe the results of treatment during treatment and after at least 15 to 30 days from the end to record the results obtained. In fact, the PGE1 acts by stimulating the endothelial cells and therefore has to be considered that the positive response is observed during administration but that is only if the skin oxygenation and blood flow in the capillaries increases and remains stable it can be stated that it has obtained a positive outcome pharmacological [5].
For this reason, patients will undergo a thorough general and specialized peripheral circulation with Echocolor Doppler, Digital Plethysmography, Capillaroscopy, evaluation of skin oxygenation in four points of the toes and hands, and retinal circulation with fluorescein angiography and it is likely, as well as already established by our personal clinical experience, which should be a period of 15-20 days after initiation of therapy, to observe the positive clinical results. The experiences of all of the various researchers who have infused PGE1 indicate that you need at least a month to get a positive clinical outcome.
Even pharmaceutical companies that sell PGE1 α Ciclodestrina recommend treatments administered intravenously for 30 days at doses of 60 μg/day. It is proposed a treatment with total dosages that contain doses of PGE1 7 (seven) times lower and dosages of L. Propionil-carnitine 50 times lower [6].
Selected treatments, drug information, preclinical and clinical trials: activity, toxicity, pharmacokinetics.
We intend to study the pharmacological action of PGE1 is associated with the L. Propionil-carnitine transported by liposomes in microangiopathies present in patients suffering from diabetes Type 1 and 2.
Preclinical experiences
1. Performed on cell cultures have shown that it was possible to get yourself a normalization of the morphology of the cells damaged by high doses of glucose in the medium (see “experiment in vivo” and Annex # 1Fase1 report cell cultures).
2. Research done on diabetic rats, infusion of PGE1 more L. Propionil-carnitine transported by liposomes has shown positive effects on endothelial cell apoptosis and tissue histology (see Annex No. 2 Fase1 report diabetic rats).
3. Research on toxicity in rats has shown that there are no toxic effects (see Annex No. 3 Fase1 Report diabetic rats).
Clinical experiences made of patients who did not respond to any medical treatment, carried out by Prof. Brotzu at the Nursing Home S. Antonio, Via Chironi 3 Cagliari in 2012. They used the same doses and the same methods of administration that are followed in the testing officer [7].
Liability of the investigator
The responsibility is generic because it is a drug treatment with drugs already tested and in use and which are known complications. Moreover, the treatment involves the use of an amount of drug substantially lower than that recommended in the instructions. Due to the low dose of PGE1 injected is impossible that suffering complications of any kind.
Bibliography
1. Marchesi S., et al. “Prostaglandin E1 improves endothelial function in critical limb ischemia”. Journal of Cardiovascular Pharmacol ogy 41.2 (2003): 249-253.
2. Mehrabi MR., et al. “Clinical and experimental evidence of Prostaglandin E1 induced angiogenesis in myocardium of patients with ischemic heart disease”. Cardiovascular Research 56.2 (2002): 214-224.
3. Mehrabi MR., et al. “Clinical benefit of Prostaglandin E1 treatment of patients with ischemic heart disease: Stimulation of thera peutic angiogenesis in vital and infarted myocardium”. Biomedicine & Pharmacotherapy 57.3 (2003): 173-178.
4. Esaki J., et al. “Local sustained release of Prostaglandin E1 induces neovascularization in Murine Hindlimb Ischemia”. Circulation Journal 73.7 (2009): 1330-1336.
5. Brotzu G., et al. “Stereo morphological arrangement of Capillaries in skeletal Muscle in Normal and stenosed young and adults rats”. Microvascular Research 27.3 (1984): 286-289.
6. Brotzu G., et al. “The stereo morphological disposition of muscular capillary network. Experimental research into the effect of training, age, arterial insufficiency and chronic treatment with EPL”. The Journal of Sports Medicine and Physical Fitness 24.1 (1984): 1-12.
7. Morezchi D., et al. “Effects of Prostaglandin E1 in the Genesis of Blood Capillaries in the Ischemic Skeletal Muscle of Rats: Ultra structural Analysis”. Annals of Vascular Surgery 22.1 (2008): 121-126.
8. Hudlicka O and Brown MD. “Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor”. Journal of Vascular Research 46.5 (2009): 504-512.
9. Kivela R., et al. “Effects of experimental type 1 diabetes on angiogenic gene expression and capillarization in skeletal muscle”. The FASEB Journal 20.9 (2006): 1570-1572.
10. Makino H., et al. “Increase in peripheral blood flow by intravenous administration of Prostaglandin E1 in patients with peripheral disease, accompanied by upregulation of hepatocytes grow factor”. Hypertension Research 27.2 (2004): 85-91.
11. Haider DG., et al. “PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells”. American Journal of Physiol ogy: Heart and Circulatory Physiology 289.5 (2005): H2066-H2072.
Source: https://www.ecronicon.com/ecps/pdf/ECPS-02-000022.pdf
Brotzu Giovanni1* and Bajamonte Myrta2
1 Professor Vascular Surgery, Cagliari Medicine University, Italy
2 Senior Clinical Embryologist Director, Palermo Medicine University, Italy
*Corresponding Author: Brotzu Giovanni, Tissue’s Micro Circle Scientific Director IVF Mediterranean Centre, Full Professor Vascular Surgery, Cagliari Medicine University, Italy.
Received: August 07, 2015; Published: September 09, 2015
Abstract
The Prostaglandin E1 and L. Propionil-carnitine are used today for the vascular disease treatment of various origin. The Prostaglandin E1 injected intravenously has a half-life is very short because metabolized predominantly by pulmonary filter and therefore does not arrive in sufficient amount in the capillaries. You have to remember that hyperglycemia impairs endothelial cells especially at the peripheral level, kidney, retina, skin microcirculation and muscle. The association PGE1 and L. Propionil-carnitine, transported by liposomes high adhesiveness not being metabolized in the lungs, is able to perform its function pharmacological on endothelial cells damaged by various diseases, such as diabetes or in TAO, especially in the capillaries where blood flow is slowed down. We intend to study the pharmacological response of our new liposomal formulation of PGE1 more L. Propionil-carnitine on peripheral microcirculation of diabetic patients presenting pathologies. Purchase new Formulation PGE1 e L. Propionil-carnitine produced by a GMP firm.
Introduction
Diabetes is a chronic disease characterized by the presence of high levels of blood glucose (hyperglycemia) and due to an altered amount or insulin function. Insulin is the hormone produced by the pancreas, which allows the glucose entry into cells and its subsequent use as an energy source. When this mechanism is altered, the glucose accumulates in the bloodstream. There are various types: Type 1 diabetes accounts for about 10% of people with diabetes and usually occurs in childhood or adolescence. For this reason, the Type 1 diabetes is classified among the diseases so-called “autoimmune”, that is due to an immune reaction directed against the body itself. Type 2 diabetes is the most common form of diabetes and represents about 90% of cases of this disease. The cause of Type 2 diabetes is unknown but characteristic is the presence in the blood of antibodies directed against antigens present at the level of insulin-producing cells, said ICA, GAD, IA-2, IA-2SS. The cause is still unknown, although it is certain that the pancreas is able to produce insulin, but the cells of the organism cannot then in use. Typically, the disease occurs after 30-40 years and many risk factors have been recognized associate to its onset. These include: the family history of diabetes, lack of exercise, being overweight and belonging to certain ethnic groups.
Type 2 diabetes usually goes undetected for many years because the hyperglycemia develops gradually and is initially not severe enough to give the classic symptoms of diabetes. Usually the diagnosis is done randomly or in conjunction with a situation of physical stress, such as infection or surgery. The risk of developing the disease increases with age, with the presence of obesity and lack of physical activity: this observation allows to predict prevention strategies “primary” that interventions can prevent the onset of the disease and that have their cornerstone in the application of a proper lifestyle, including nutritional and exercise. Gestational diabetes: Gestational diabetes is defined every situation in which a high level of measuring circulating glucose for the first time during pregnancy. This condition occurs in about 4% of pregnancies. The definition is independent of the type of treatment used, it’s just the dietary or the need for insulin and implies a higher frequency of checks for pregnant and the fetus. The symptoms of the onset of the disease depend on the type of diabetes. In the case of Type 1 diabetes usually are witnessing an acute onset, often in connection with a febrile episode, with thirst polydipsia), increased amounts of urine (polyuria), is feeling fatigue (asthenia), weight loss, dry skin, increased frequency of infections.
In Type 2 diabetes, however, the symptoms are more nuanced and usually do not allow a quick diagnosis, so often your blood sugar is high but without clinical signs of Type 1 diabetes. Diabetes can cause acute or chronic complications. Acute complications are more common in Type 1 diabetes and are related to the almost total lack of insulin. In these cases, the patient may experience ketoacidosis coma, due to accumulation of products of altered metabolism, ketones which cause loss of consciousness, dehydration and serious blood disorders. In Type 2 diabetes acute complications are rare, but are very frequent chronic complications that affect different organs and tissues, including the eyes, kidneys, heart, blood vessels and peripheral nerves. The complications of diabetes is Type 1 and 2 are:
1. Diabetic retinopathy: is damage to the small blood vessels that supply the retina with loss of the sight. In addition, people with diabetes are more likely to develop eye diseases such as glaucoma and cataracts.
2. Diabetic nephropathy: it is a gradual reduction of the filter function of the kidney that, if left untreated, can lead to renal insufficiency up to the need for dialysis and/or kidney transplant.
3. Cardiovascular disease: the risk of cardiovascular disease is 2 to 4 times higher in people with diabetes than in the general population resulting in industrialized countries, more than 50% of deaths from diabetes. This leads us to consider the cardiovascular risk in diabetic patients equal to that given to a patient who had a cardiovascular event
4. Diabetic neuropathy: is one of the most frequent complications and according to the World Health Organization is manifested at different levels in 50% of diabetics. It can cause loss of feeling, pain of varying intensity and limb injuries, requiring amputation in severe cases. Can lead to malfunctions of the heart, eyes, stomach and is one of the main causes of male impotence.
5. Diabetic foot: the modifications of the structure of blood vessels and nerves can cause ulceration and problems in the lower limbs, especially the foot, due to loads that. This may necessitate the amputation of limbs and statistically is the leading cause of lower limb amputation for non-traumatic
6. Complications in pregnancy: pregnant women, diabetes can result in adverse consequences on the fetus, congenital malformations with a high birth weight, up to a high risk of perinatal mortality. The high frequency of vascular complications requiring close monitoring of target organs (eyes, kidneys and lower limbs). For this reason, it is necessary for people with diabetes to undergo regular check-ups, even in the absence of symptoms.
Microcirculation refers to the blood circulation in the capillaries and agree that the diameter of these vessels go from 40 to 5 micra. At the beginning of the capillaries from the arterial side there are muscular structures, called pericytes, which regulate the flow while in most peripheral level the capillaries and from the venous side are constituted only by endothelial cells. Microangiopathy is a disease that affects the microcirculation and this being different from organ to organ there are several types of microangiopathy. The diabetes affects the endothelial cells throughout the body causing different diseases.
Microangiopathy is a disease in diabetic patients and it is installed over time and therefore can be considered a chronic disease. At the level of the microcirculation hyperglycemia causes:
1. Increased apoptosis of endothelial cells;
2. The decreased ability of reproduction of endothelial cells;
3. The increase of endothelin which reduces the diameter of the capillaries;
4. Slow blood flow in the capillaries;
The consequence of the above phenomena is primarily tissue oxygenation decrease. The theoretical basis for the use of prostaglandins in Critical Limb Ischemia (CLI) are well known [1]. The Prostaglandin E1 and Prostacyclin expand and improve the local flow. The prostaglandin E1 has an angiogenic and anti-inflammatory effect and improves endothelial function. The PGE1 stimulates endothelial cells VEGF receptors and facilitates the reproduction to maintain sufficient capillarization in the tissue. The problem existing is that Prostaglandin E1 injected intravenously has a half-life very short (less 1 min.) because metabolised predominantly by pulmonary filter and therefore does not arrive in sufficient amount in the capillaries, and the amount injected in increased there are side effects (tachycardia, hypotension, etc.). In fact, the therapeutic administration of PGE1 causes a vasodilatation but also a marked hypotension. Both PGE1 that Iloprost, Prostacyclin analogue, have been evaluated in several clinical trials in patients with CLI. The results of all these studies have failed to demonstrate the true clinical utility of the treatment of arterial disease with prostanoids. Treatment with PGE1 has been approved by the Min of Health, as already mentioned, has never had much success. For that reason have been proposed Prostacyclin analogs that have a half-life greater (Iloprost). But also this search and was performed on patients with systolic pressures at the level of the tibial lower than 50 mmHg and not in patients with microangiopathy and gave results somewhat uncertain [2].
In 1991, our group experienced the treatment of microangiopathy of different origin, IIb and stage III sec. Fontaine (diabetic, from connective tissue, and in Buerger’s disease) with a continuous Iloprost infusion, via elastomeric pump, for a period of 28 days. The results of these studies we did observe that it was possible to obtain a marked improvement of symptoms due to microangiopathy. Infusion therapy with prostanoids was used both before and after surgical revascularization [3]. The goal of therapy was to reduce the phenomena closely related to microangiopathy.
In fact therapy with Iloprost or with PGE1 causes vasodilation, reduces platelet aggregation and restores the functions of endothelial tissue, but is not able to increase the flow in the presence of stenosis or obstruction of macrocirculation. The PGE1 has, as has already been said, a short half-life, but that compared to Iloprost, has the advantage of better reactivate the system functionality endothelial, acting on the VEGF receptor, and at the same time causes a marked vasodilation and if injected directly into the artery in the districts with decreased blood flow causes a marked peripheral vasodilation. But this practice cannot be used for a routine treatment. If injected intravenously its short half-life, lower per minute limits its therapeutic action. By some researchers has been observed that the therapeutic effect improves when PGE1 is associated together with the l-propionyl-carnitine in the treatment of microangiopathies of various origin and in Buerger’s disease to stage II or III. To determine a pharmacological action on the microcirculation, damaged by diabetic pathology, it has been proposed to carry the PGE1 from liposomes that cross the pulmonary filter and have the characteristic of adhering to endothelial cells, especially in sites where there is a microangiopathy and blood flow slows down, and for a low blood pressure and because the endothelial cells are damaged by diabetes [4].
The new formulation was performed at the Department of Chemistry and pharmaceutical technology direct from Prof. Fadda. (See attachment # 1 chemical and physical exam). The liposomes of phosphatidylcholine have the ability to overcome the filter lung to adhere to the endothelial cells of the capillaries species in districts where the blood flow is slowed down and release the drug directly at the level of the peripheral microcirculation.
In the experiments performed in diabetic rats with streptozocin we observed that the administration of liposomes coated with polylysine containing PGE1 more L. Propionil-carnitine determined compared to untreated rats:
1. Decrease endothelial apoptosis in the kidneys in the lungs in the muscle
2. Increase of VEGF
3. Lower water consumption, and better renal function
These observations lead us to propose the use of PGE1 α-cyclodextrin and L. Propionil carnitine transported by liposomes of phosphatidylcholine coated with polylysine in clinical use for the treatment of diabetic foot and microangiopathy in general.
Objectives
The objective of the study is to demonstrate that administration of PGE1 together with L. Propionil-carnitine transported by liposomes is able to determine the healing or at least a net improvement of microangiopathies induced by diabetes. In particular, we wish to observe whether it is possible to obtain a result pharmacological stable over time.
Material and Methods
Because diabetic microangiopathy are chronic diseases is essential to observe the results of treatment during treatment and after at least 15 to 30 days from the end to record the results obtained. In fact, the PGE1 acts by stimulating the endothelial cells and therefore has to be considered that the positive response is observed during administration but that is only if the skin oxygenation and blood flow in the capillaries increases and remains stable it can be stated that it has obtained a positive outcome pharmacological [5].
For this reason, patients will undergo a thorough general and specialized peripheral circulation with Echocolor Doppler, Digital Plethysmography, Capillaroscopy, evaluation of skin oxygenation in four points of the toes and hands, and retinal circulation with fluorescein angiography and it is likely, as well as already established by our personal clinical experience, which should be a period of 15-20 days after initiation of therapy, to observe the positive clinical results. The experiences of all of the various researchers who have infused PGE1 indicate that you need at least a month to get a positive clinical outcome.
Even pharmaceutical companies that sell PGE1 α Ciclodestrina recommend treatments administered intravenously for 30 days at doses of 60 μg/day. It is proposed a treatment with total dosages that contain doses of PGE1 7 (seven) times lower and dosages of L. Propionil-carnitine 50 times lower [6].
Selected treatments, drug information, preclinical and clinical trials: activity, toxicity, pharmacokinetics.
We intend to study the pharmacological action of PGE1 is associated with the L. Propionil-carnitine transported by liposomes in microangiopathies present in patients suffering from diabetes Type 1 and 2.
Preclinical experiences
1. Performed on cell cultures have shown that it was possible to get yourself a normalization of the morphology of the cells damaged by high doses of glucose in the medium (see “experiment in vivo” and Annex # 1Fase1 report cell cultures).
2. Research done on diabetic rats, infusion of PGE1 more L. Propionil-carnitine transported by liposomes has shown positive effects on endothelial cell apoptosis and tissue histology (see Annex No. 2 Fase1 report diabetic rats).
3. Research on toxicity in rats has shown that there are no toxic effects (see Annex No. 3 Fase1 Report diabetic rats).
Clinical experiences made of patients who did not respond to any medical treatment, carried out by Prof. Brotzu at the Nursing Home S. Antonio, Via Chironi 3 Cagliari in 2012. They used the same doses and the same methods of administration that are followed in the testing officer [7].
Liability of the investigator
The responsibility is generic because it is a drug treatment with drugs already tested and in use and which are known complications. Moreover, the treatment involves the use of an amount of drug substantially lower than that recommended in the instructions. Due to the low dose of PGE1 injected is impossible that suffering complications of any kind.
Bibliography
1. Marchesi S., et al. “Prostaglandin E1 improves endothelial function in critical limb ischemia”. Journal of Cardiovascular Pharmacol ogy 41.2 (2003): 249-253.
2. Mehrabi MR., et al. “Clinical and experimental evidence of Prostaglandin E1 induced angiogenesis in myocardium of patients with ischemic heart disease”. Cardiovascular Research 56.2 (2002): 214-224.
3. Mehrabi MR., et al. “Clinical benefit of Prostaglandin E1 treatment of patients with ischemic heart disease: Stimulation of thera peutic angiogenesis in vital and infarted myocardium”. Biomedicine & Pharmacotherapy 57.3 (2003): 173-178.
4. Esaki J., et al. “Local sustained release of Prostaglandin E1 induces neovascularization in Murine Hindlimb Ischemia”. Circulation Journal 73.7 (2009): 1330-1336.
5. Brotzu G., et al. “Stereo morphological arrangement of Capillaries in skeletal Muscle in Normal and stenosed young and adults rats”. Microvascular Research 27.3 (1984): 286-289.
6. Brotzu G., et al. “The stereo morphological disposition of muscular capillary network. Experimental research into the effect of training, age, arterial insufficiency and chronic treatment with EPL”. The Journal of Sports Medicine and Physical Fitness 24.1 (1984): 1-12.
7. Morezchi D., et al. “Effects of Prostaglandin E1 in the Genesis of Blood Capillaries in the Ischemic Skeletal Muscle of Rats: Ultra structural Analysis”. Annals of Vascular Surgery 22.1 (2008): 121-126.
8. Hudlicka O and Brown MD. “Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor”. Journal of Vascular Research 46.5 (2009): 504-512.
9. Kivela R., et al. “Effects of experimental type 1 diabetes on angiogenic gene expression and capillarization in skeletal muscle”. The FASEB Journal 20.9 (2006): 1570-1572.
10. Makino H., et al. “Increase in peripheral blood flow by intravenous administration of Prostaglandin E1 in patients with peripheral disease, accompanied by upregulation of hepatocytes grow factor”. Hypertension Research 27.2 (2004): 85-91.
11. Haider DG., et al. “PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells”. American Journal of Physiol ogy: Heart and Circulatory Physiology 289.5 (2005): H2066-H2072.
Source: https://www.ecronicon.com/ecps/pdf/ECPS-02-000022.pdf
- Reaction score
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Brotzu lotion cured chronic constipation.
He went to put some pomade on the Brotzu lotion created hair
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My unbiased insane opinion is that Brotzu is unloading all the Finasteride where it belongs, with a huge pile of sh*t.
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Here's my dilemma with the entire Brotzu lotion theory:
We already have a way to increase PGE1. minoxidil. Doesn't stop miniaturisation or loss. So then we get into 5AR's. Sure, equol seems to be a decent 5AR, but we already have those too. Mostly they aren't that effective. Carnitine has been done. I've been there myself. So we already have things with all the same mechanisms of action which at the end of the day, don't really help us. So how is this lotion based upon all the old premises that we've tried and failed with going to work better than minoxidil/fina/duta?
Dr. Brotzu has stated in interviews that the golden key to the formula is the liposome vehicle, and without it the product wouldn't be effective. It penetrates extremely well and holds the ingredients at the hair follicle.
A liposome vehicle is what Hasson and Wong use for their topical finasteride since they also claim it penetrates very well while staying in the dermis.
I don't think a lot of people realize how important liposomes are.
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as this sh*t (hairloss) is complicated Im a big believer in "all in one" treatment or let's say treatment targeting different angles (like follica). If all these ingredients are used together effectiveness is different. it's like the big 3: it does the job but take minoxidil alone that will be a different story, even fina alone sometimes is not enough for some people. And don't forget another important point : the vehicle. people at home who make their own preparation often use the "by default" vehicle like alcholol/water etc but that's often not enough to make a stable/effective preparation you need a lot of ingredients to make it a good product and at the right percentage
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r/tresless is getting more ridiculous every minute we close in on the presentation. Even though I am very much optimistic I do worry for people's mental state if they get disappointed. Let's pray for the Brotion Overlords!