Ostela

Uses

Chondroitin sulfate, used with glucosamine, is indicated to alleviate pain and inflammation from primary osteoarthritis. This supplement is reported to improve joint function and slow disease progression. Osteoarthritis is characterized by progressive structural and metabolic changes in joint tissues, mainly cartilage degradation, subchondral bone sclerosis and inflammation of synovial membrane.

Studies have proposed the potential use of chondroitin sulfate as a nutraceutical in dietary supplements.

Magnesium is a medication used for many purposes including constipation, indigestion, magnesium deficiency, and pre-eclampsia.

Healthy levels of magnesium can be achieved through a well balanced diet, but if food sources are insufficient, magnesium supplements can be used to prevent and treat magnesium deficiencies.

In medicine, various magnesium salts may be used in laxative and antacid products. For example, magnesium citrate is available over-the-counter and may be used to manage occasional constipation. Magnesium sulfate may be used on its own or with total parenteral nutrition to treat hypomagnesemia. Magnesium sulfate is also indicated to prevent seizures in pregnant women with pre-eclampsia, and to manage seizures associated with eclampsia.

Manganese is a transition metal used for supplementation of manganese during Total Parenteral Nutrition (TPN).

Indicated for use as a supplement to intravenous solutions given for Total Parenteral Nutrition (TPN). Administration helps to maintain plasma levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

Zinc is an essential element commonly used for the treatment of patients with documented zinc deficiency.

Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .

Ostela is also used to associated treatment for these conditions: Arthritis, Backache, Muscle Strain, Osteoarthritis (OA), Soreness, Muscle, Sprains, Eye lubrication, Joint supplementationCalcium Deficiency, Magnesium Deficiency, Zinc DeficiencyMineral supplementation, Total parenteral nutrition therapy, Vitamin supplementation, Dietary supplementationCandidiasis, Common Cold, Diaper Dermatitis, Diaper Rash, Eye redness, Iron Deficiency (ID), Ocular Irritation, Skin Irritation, Sunburn, Wilson's Disease, Zinc Deficiency, Dietary and Nutritional Therapies, Dietary supplementation

How Ostela works

Chondroitin sulfate functions as a major component of the intricate extracellular matrix. It is proposed that chondroitin sulfate supply can provide new building blocks for the synthesis of new matrix components.

The anti-inflammatory effect of chondroitin sulfate is thought to be caused by the inhibition of the synthesis of inflammatory intermediates such as the inhibition of nitric oxide synthase, COX-2, microsomal prostaglandin synthase 1 and prostaglandin E2. It is reported also an inhibitory activity in the toll-like receptor 4 which will later inhibit inflammatory cytokines, NFkB and MyD88. This activity suggests a modulation of the MAP kinase pathway. On the other hand, some reports have pointed out an induction on the PKC/PI3K/Akt pathway in neuroblastoma.

The anabolic effect of chondroitin sulfate is suggested to be caused by the inhibition of metalloproteinases such as MMP-1, -3 and -13 as well as ADAMTS-4 and -5.

Magnesium is a cofactor for at least 300 enzymes and is important for several functions in the body with some key processes identified below. Enzymes that rely on magnesium to operate help produce energy through oxidative phosphorylation, glycolysis and ATP metabolism. They are also involved in nerve function, muscle contraction, blood glucose control, hormone receptor binding, protein synthesis, cardiac excitability, blood pressure control, gating of calcium channels and transmembrane ion flux.

The mitochondrial intracellular space is rich in magnesium, since it is required to produce the active form of ATP (adenosine triphosphate) from ADP (adenosine diphosphate) and inorganic phosphate, and behaves as a counter ion for the energy rich molecule. Additionally, magnesium is essential for ATP metabolism.

Zinc has three primary biological roles: catalytic, structural, and regulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .

Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .

In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .

There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .

Zinc deficiency in humans decreases the activity of serum thymulin (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans [A342417].

The change of Th(1) to Th(2) function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells [A3424].

In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .

In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers [A3424]. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .

The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .

Toxicity

Chondroitin sulfate does not present a carcinogenic potential. On tolerability assays, it has been shown to present great safety and good tolerability without significant severe side effects.

The recommended dietary allowance of magnesium ranges from 30 mg for infants to 420 mg for males between the age of 31 and 50. According to the institute of Medicine (IOM), the majority of adults can tolerate 350 mg of magnesium per day without experiencing adverse effects. Symptoms of magnesium toxicity include diarrhea and other gastrointestinal effects, thirst, muscle weakness, drowsiness, severe back and pelvic pain, hypotension, dizziness, confusion, difficulty breathing, lethargy, and deterioration of kidney function. Other more severe symptoms associated with magnesium overdose include loss of consciousness, respiratory arrest, cardiac arrhythmias and cardiac arrest.

Regular use of laxatives containing magnesium may lead to severe and even fatal hypermagnesemia.

Discontinuation of magnesium products including supplements, laxatives, and antacids is usually sufficient to manage mild cases of magnesium overdose; however, patients should also be screened for renal impairment.

In severe cases of magnesium overdose, patients may require supportive care and interventions including intravenous fluids and furosemide, IV calcium chloride or calcium gluconate, renal dialysis and artificial respiratory support.

According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury .

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice .

Volume of Distribution

After intramuscular administration of chondroitin sulfate, the apparent volume of distribution was 0.40 ml/g. When administered orally, the apparent volume of distribution changed to 0.44ml/g.

According to a pharmacokinetic review, the volume of distribution of magnesium sulphate when used to manage patients with pre-eclampsia and eclampsia ranged from 13.65 to 49.00 L.

A pharmacokinetic study was done in rats to determine the distribution and other metabolic indexes of zinc in two particle sizes. It was found that zinc particles were mainly distributed to organs including the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender .

Elimination Route

Chondroitin sulfate is absorbed from the gastrointestinal tract. The absorbed portion reaches a ratio of 10% as unchanged chondroitin sulfate and 90% as depolymerized low-molecular-weight derivatives. This absorption depends on the sulfation status. The bioavailability of chondroitin sulfate ranges from 10-20% following oral administration. Reports have shown a consistent accumulation of the compound in joint tissue. The steady-state is attained after 3-4 days and it takes around 3-6 months to obtain the maximal effect.

After intramuscular administration of chondroitin sulfate, the peak plasma level of 3.8 mcg/ml was reached after 90 min. When given orally, the peak plasma concentration of 4.6 mcg/ml was reached after 240 min.

Approximately 24-76% of ingested magnesium is absorbed in the gastrointestinal tract, primarily via passive paracellular absorption in the small intestine.

Zinc is absorbed in the small intestine by a carrier-mediated mechanism . Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition .

Generally, 33% is considered to be the average zinc absorption in humans . More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].

Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption .

Half Life

The approximate half-life of chondroitin sulfate and its derivative metabolites is 15 hours. After intramuscular administration of chondroitin sulfate in humans, the elimination half-life of the chondroitin sulfate was of 275 min. When administered orally, the elimination half-life was presented at 310 min.

Magnesiums biologic half-life is reported to be approximately 1000 hours or 42 days.

The half-life of zinc in humans is approximately 280 days .

Clearance

In one study of healthy patients, the clearance of zinc was found to be 0.63 ± 0.39 μg/min .

Elimination Route

Chondroitin sulfate is excreted in the urine as intact polymers and as partial degradation products. After intramuscular administration, about 37% of the administered dose is excreted by urine during the first 24 hours as high- and low-molecular-weight derivatives.

The majority of magnesium is excreted renally.

The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body .

Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) .

Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed .

Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need .

In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces .

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