Nuprosan

Uses

Alanine is an amino acid commonly found as a component of total parenteral nutrition.

Used for protein synthesis.

Arginine is an amino acid commonly found as a component of total parenteral nutrition.

Used for nutritional supplementation, also for treating dietary shortage or imbalance.

Aspartic acid is an amino acid commonly found as a component in total parenteral nutrition.

There is no support for the claim that aspartates are exercise performance enhancers, i.e. ergogenic aids.

Cysteine is an amino acid commonly found as a component of total parenteral nutrition and used as an antidote for acetaminophen overdose.

For the prevention of liver damage and kidney damage associated with overdoses of acetaminophen

Glutamic acid is an amino acid commonly found as a component in total parenteral nutrition.

Considered to be nature's "Brain food" by improving mental capacities; helps speed the healing of ulcers; gives a "lift" from fatigue; helps control alcoholism, schizophrenia and the craving for sugar.

This is used for irrigating fluid of choice in:

• Transurethral resection of prostate.
• Endoscopic procedures within the urinary tract.
• Urinary bladder surgery etc.

Histidine is an amino acid commonly found as a component of total parenteral nutrition.

The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.

Isoleucine is an amino acid commonly found as a component of total parenteral nutrition.

The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.

Leucine is an amino acid commonly found as a component of total parenteral nutrition.

Indicated to assist in the prevention of the breakdown of muscle proteins that sometimes occur after trauma or severe stress.

Methionine is an amino acid commonly found as a component in total parenteral nutrition.

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

Phenylalanine is an amino acid commonly found as a component of total parenteral nutrition.

L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.

Proline is an amino acid commonly found as a component of total parenteral nutrition.

L-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.

Serine is an amino acid commonly found as a component in total parenteral nutrition.

Used as a natural moisturizing agent in some cosmetics and skin care products.

Threonine is an amino acid commonly found as a component of total parenteral nutrition.

L-Threonine makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

Tryptophan is an amino acid commonly found as a component of total parenteral nutrition.

Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

Tyrosine is an amino acid commonly found as a component in total parenteral nutrition.

Tyrosine is claimed to act as an effective antidepressant, however results are mixed. Tyrosine has also been claimed to reduce stress and combat narcolepsy and chronic fatigue, however these claims have been refuted by some studies.

Nuprosan is also used to associated treatment for these conditions: Amino acid supplementationAcromegaly, Gigantism, Hyperammonaemia, Hypophysectomy, Kidney Damage, Panhypopituitarism, Pituitary Dwarfism, Pituitary Neoplasms, Deficiencies in enzymes of the urea cycle, Pituitary trauma, Postsurgical craniopharyngioma, Problems of growth and stature, Nutritional supplementation, Amino acid supplementationAmino acid supplementationTotal parenteral nutrition therapy, Amino acid supplementationAmino acid supplementationCoronary vascular graft occlusion, Deep Vein Thrombosis, Myocardial Infarction, Stroke, Transient Ischemic Attack, Vascular Occlusion, Bladder distension, Bladder irrigation therapy, Irrigation therapy, Recovery, Amino acid supplementationAmino acid supplementationAmino acid supplementationHypoalbuminemia, Amino acid supplementationHepatic Encephalopathy (HE), Amino acid supplementationAmino acid supplementationAmino acid supplementationIron Deficiency (ID), Iron Deficiency Anemia (IDA), Amino acid supplementationAmino acid supplementationAcute Renal Failure (ARF), Chronic Renal Failure (CRF), Depression, Dialysis therapy, Dietary and Nutritional Therapies, Amino acid supplementationChronic Renal Failure (CRF), Acute Renal Dysfunction, Amino acid supplementation

How Nuprosan works

L-Alanine is a non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. BCAAs are used as a source of energy for muscle cells. During prolonged exercise, BCAAs are released from skeletal muscles and their carbon backbones are used as fuel, while their nitrogen portion is used to form another amino acid, Alanine. Alanine is then converted to Glucose by the liver. This form of energy production is called the Alanine-Glucose cycle, and it plays a major role in maintaining the body's blood sugar balance.

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt, spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in the Krebs cycle and for stimulating the purine nucleotide cycle.

Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Cysteine is typically synthesized in the human body when there is sufficient methionine available. Cysteine exhibits antioxidant properties and participates in redox reactions. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. Glutathione (GSH) typically requires biosynthesis from its constituent amino acids, cysteine, glycine, and glutamic acid, due to its limited systemic availability. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. In human metabolism, cysteine is also involved in the generation of sulfide present in iron-sulfur clusters and nitrogenase by acting as a precursor. In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).

Glutamate activates both ionotropic and metabotropic glutamate receptors. The ionotropic ones being non-NMDA (AMPA and kainate) and NMDA receptors. Free glutamic acid cannot cross the blood-brain barrier in appreciable quantities; instead it is converted into L-glutamine, which the brain uses for fuel and protein synthesis. It is conjectured that glutamate is involved in cognitive functions like learning and memory in the brain, though excessive amounts may cause neuronal damage associated in diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. Also, the drug phencyclidine (more commonly known as PCP) antagonizes glutamate at the NMDA receptor, causing behavior reminiscent of schizophrenia. Glutamate in action is extremely difficult to study due to its transient nature.

In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia.
Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.

Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints.
L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis.
This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.

The supposed antidepressant effects of L-phenylalanine may be due to its role as a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin

Glycogenic, by L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde. It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.

L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present.

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD⁺ and NADP⁺.

Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%. The mechanism of L-tyrosine's antidepressant activity can be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.

Dosage

Nuprosan dosage

The total volume of solution used for irrigation depends on the judgment of the attending surgeon. Height from the operating table of 60 cm (approx. 2ft) is likely to cause increased intravascular absorption of glycine.

• Check infusion set and infusion solution prior to use
• Pull moderately to tear off the protective cover of the Eurohead
• Hold lightly the Eurohead but not the bag
• Open the flow regulator fully and hold the giving set on the top white area, but not the membrane venting region
• Insert the spike of the administration set to the Eurohead and fit the connector of the administration set firmly to the needle
• Gradually allow the fluid to flow down to the needle tip and close
• Remove the protective cover of the needle
• Locate the veinpuncture site and clean the site with an antiseptic solution, and then insert the needle
• Securely tape the puncture site
• Securely tape the wings and tubing
• Start infusion while adjusting drip speed

Side Effects

Large intravenous doses of glycine are known to cause nausea and salivation. Other consequences of systemic absorption of glycine include electrolyte loss, diuresis, edaema, thirst, dehydration, cardiovascular and pulmonary disorders.

Toxicity

Oral supplementation with L-arginine at doses up to 15 grams daily are generally well tolerated. The most common adverse reactions of higher doses from 15 to 30 grams daily are nausea, abdominal cramps and diarrhea. Some may experience these symptoms at lower doses.

Mild gastrointestinal side effects including diarrhea. LD₅₀ (rat) > 5,000 mg/kg.

Glutamate causes neuronal damage and eventual cell death, particularly when NMDA receptors are activated, High dosages of glutamic acid may include symptoms such as headaches and neurological problems.

ORL-RAT LD₅₀ 7930 mg/kg, SCU-RAT LD₅₀ 5200 mg/kg, IVN-RAT LD₅₀ 2600 mg/kg, ORL-MUS LD₅₀ 4920 mg/kg; Doses of 1 gram daily are very well tolerated. Mild gastrointestinal symptoms are infrequently noted. In one study doses of 90 grams daily were also well tole.

ORL-RAT LD₅₀ > 15000 mg/kg, IPR-RAT LD₅₀ > 8000 mg/kg, ORL-MUS LD₅₀ > 15000 mg/kg, IVN-MUS LD₅₀ > 2000 mg/kg; Mild gastrointestinal side effects.

Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs

Doses of L-methionine of up to 250 mg daily are generally well tolerated. Higher doses may cause nausea, vomiting and headache. Healthy adults taking 8 grams of L-methionine daily for four days were found to have reduced serum folate levels and leucocytosis. Healthy adults taking 13.9 grams of L-methionine daily for five days were found to have changes in serum pH and potassium and increased urinary calcium excretion. Schizophrenic patients given 10 to 20 grams of L-methionine daily for two weeks developed functional psychoses. Single doses of 8 grams precipitated encephalopathy in patients with cirrhosis.

L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.

Oral rat LD₅₀: > 16 gm/kg. Investigated as a tumorigen, mutagen, reproductive effector. Symptoms of overdose include agitation, confusion, diarrhea, fever, overactive reflexes, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, twitching, and vomiting.

L-Tyrosine has very low toxicity. There have been very few reports of toxicity. LD₅₀ (oral, rat) > 5110 mg/kg.

Precaution

Precautions: Patients with cardiovascular disease should be evaluated after transurethral resection of prostate using glycine. Care should be exercised if the liver or kidney is impaired.

Warning: Aseptic technique is essential while using glycine. Unused portion should be discarded. Do not use if the bottle is leaking, solution is cloudy, contains particles or after expiry date.

Interaction

Additives may be incompatible. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Elimination Route

Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.

Absorbed from the small intestine by an active transport process

Absorbed from the lumen of the small intestine into the enterocytes.Absorption is efficient and occurs by an active transport mechanism.

Absorbed from the small intestine via an active transport mechanism.

Absorbed from the small intestine via an active transport mechanism requiring the presence of sodium.

Absorbed from the small intestine by a sodium-dependent active-transport process

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

Absorbed from the small intestine by a sodium dependent active transport process.

L-tyrosine is absorbed from the small intestine by a sodium-dependent active transport process.

Contraindication

Glycine Irrigation Solution is not for injection in any route. It is contraindicated in patients with anuria.

Storage Condition

Store at controlled room temperature, protect from light and heat

Innovators Monograph

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