Crazy Bulk Review – Detailed and HonestTo explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn blue dragon labs steroids. Severe burn causes exaggerated muscle protein catabolism, contributing to weakness and delayed healing. Oxandrolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS ethyl burn 180 anabolic. Fourteen severely burned children were enrolled during a 5-month period in a prospective cohort analytic study. There was a prolonged delay in the arrival of these patients to the burn unit ethyl burn 180 anabolic definitive care. This neglect of skin grafting and nutritional support resulted in critically ill children with significant malnutrition.
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To explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn patients. Severe burn causes exaggerated muscle protein catabolism, contributing to weakness and delayed healing.
Oxandrolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS patients. Fourteen severely burned children were enrolled during a 5-month period in a prospective cohort analytic study. There was a prolonged delay in the arrival of these patients to the burn unit for definitive care. This neglect of skin grafting and nutritional support resulted in critically ill children with significant malnutrition.
On arrival, all patients underwent excision and skin grafting and received similar clinical care. Subjects were studied 5 to 7 days after admission, and again after 1 week of oxandrolone treatment at 0. Muscle protein kinetics were derived from femoral arterial and venous blood samples and vastus lateralis muscle biopsies during a stable isotope infusion. Control and oxandrolone subjects were similar in age, weight, and percentage of body surface area burned. Muscle protein net balance decreased in controls and improved in the oxandrolone group.
The improvement in the oxandrolone group was associated with increased protein synthesis efficiency. Muscle protein breakdown was unchanged. In burn victims, oxandrolone improves muscle protein metabolism through enhanced protein synthesis efficiency. These findings suggest the efficacy of oxandrolone in impeding muscle protein catabolism in cachectic, critically injured children.
Severe burns induce marked physiologic derangements in addition to skin injury. These include hypermetabolism with erosion of lean body mass, generalized weakness, altered immune function with increased infectious complications, peripheral insulin resistance, and poor wound healing. To avert hypermetabolism, pharmacologic agents have been used to stimulate growth and increase strength after burn. Recombinant human growth hormone has shown efficacy in improving muscle protein kinetics 14—17 and wound healing, 18—20 and also in lowering the death rate in severely burned patients.
At low doses, its action is directed at attenuating protein breakdown, but at higher doses it primarily affects protein synthesis.
Testosterone can increase protein synthesis, 27 but its use entails risks of virilism and hepatotoxicity. Oxandrolone, an oral synthetic testosterone analog, has been used in acute and rehabilitating adult burn patients with promising results in terms of weight gain and urinary nitrogen balance.
The purpose of our study was to determine whether oxandrolone would affect burn-induced catabolism—in other words, would it improve the net balance of muscle protein synthesis and breakdown—and if so, by what mechanism. As an international tertiary referral center for children with severe burns, we receive many patients who are weeks removed from their injury.
These patients arrive without definitive surgical treatment or adequate nutritional support. Burn wound sepsis or chronic eschar colonization is frequent. We chose to study this subpopulation of burn victims because they shared a similar therapeutic indication depleted nutritional status with patients who had received oxandrolone in previous studies.
Inclusion criteria were as follows: All subjects were admitted to the Shriners Burns Hospital for Children in Galveston, Texas, at least one week after injury. Within 48 hours of admission, each patient underwent total burn wound excision and grafting with autograft skin and allograft.
Patients were returned to the operating room when autograft donor sites healed and became available for reharvest usually 6—10 days. Sequential staged surgical procedures for repeat excision and grafting were undertaken until the wounds were healed. This feeding regimen was started at admission and continued at a constant rate until the wounds were healed. Caloric intake remained constant throughout the study periods.
Patients were at bed rest after excision and grafting procedures for 5 days. After this, patients ambulated daily until the next excision and grafting procedure. Patients were treated in an identical fashion in terms of mobilization and rehabilitation in both study periods. From February through July , 14 patients were enrolled in a prospective cohort analytic series. The first seven received oxandrolone treatment, and the next seven served as time controls. After the first surgical procedure, all patients were studied on postoperative day 5 to determine baseline protein metabolism Fig.
Net phenylalanine balance across the leg and the fractional synthetic rate FSR of skeletal muscle protein were measured as main outcome variables. When the donor sites healed at 6 to 10 days, patients were returned to the operating room for another excision and grafting procedure. After the second surgical procedure, patients in the drug treatment group received oxandrolone 0. A second series of protein kinetic studies was performed on postoperative day 5 after the second surgical procedure to determine any differences with oxandrolone treatment or time between the drug and control patients.
Burn wounds were totally excised and grafted within 48 hours of admission. After 5 days, a baseline muscle protein kinetic study was done. After the second serial grafting procedure, patients in the control and drug groups underwent a 5-day treatment period and then were studied again.
It was administered by mouth to the patients in the drug treatment group if tolerated. Otherwise, the oxandrolone tablet was crushed and suspended in 2 mL ethanol. This suspension was then injected into the nasoduodenal tube, followed by a mL flush of sterile water.
On postoperative day 5, all patients underwent a 5-hour protein kinetic study Fig. Baseline blood samples were obtained from an indwelling femoral arterial or central venous catheter for background amino acid enrichment and systemic indocyanine green ICG concentrations.
Because phenylalanine is not synthesized or degraded in the peripheral tissues it is metabolized only in the liver , measurement across the leg reflects the net balance of protein synthesis and breakdown.
The muscle biopsies were performed using a Bergstrom needle Depuy, Chicago, IL attached to a suction device. Between hours 3 and 4, leg blood flow was determined by ICG infusion infusion rate 0.
Blood samples from the femoral and subclavian veins were taken simultaneously every 15 minutes for this determination. Between hours 4 and 5, blood samples were obtained from the femoral artery and vein to determine arteriovenous phenylalanine concentration differences across the leg.
After the last muscle biopsy, the stable isotope infusion was stopped. Catheters were left in place for use at the next excision and grafting procedure. Five-hour isotope infusion protocol. Beginning between 5 and 7 am, subjects in the continuously fed state were infused with a prime-constant d 5 -phenylalanine isotope. Indocyanine green dye concentration was measured between hours 3 and 4 to determine leg blood flow.
Femoral arteriovenous sampling during the fifth hour measured cross-leg phenylalanine balance. Muscle biopsies were performed at 2 and 5 hours while subjects were under intravenous conscious sedation. The blood concentration of unlabeled phenylalanine and the enrichment of its isotopic counterpart were simultaneously determined by gas chromatography—mass spectrometry using the internal standard approach and the nitrogen-acetyl- n -propyl esters, as previously described.
The samples were deproteinized with sulfosalicylic acid and centrifuged, and the supernatant was processed to form nitrogen-acetyl- n -propyl esters. Tissue biopsies of the vastus lateralis were immediately blotted and frozen in liquid nitrogen. In this process, an internal standard containing 5. The tissues were then homogenized and centrifuged, and the supernatant fluid was processed as described for the plasma samples above.
Arterial and venous amino acid concentrations were determined in heparinized plasma at 4 and 5 hours of the isotope infusion study.
Amino acid concentrations were determined by high-performance liquid chromatography. On the morning of both the baseline and treatment studies, 13 mL whole blood was drawn from the patient and sent for a liver function panel, a nutrition panel, and coagulation times.
The liver panel and nutrition panels were sent in nonheparinized tubes and centrifuged at 2, rpm for 10 minutes. The coagulation panel was sent in a citrated blood tube and centrifuged at 4, rpm for 10 minutes to separate the plasma fraction. Energy expenditure was measured by indirect calorimetry. Between 2 and 5 am on the day of study in both the baseline and treatment periods, CO 2 production, O 2 uptake, respiratory quotient, and resting energy expenditure were measured with a standard metabolic cart Sensormedics Model , Yorba Linda, CA.
The infusion rate was known 0. Leg amino acid kinetics were calculated according to a three-compartment model, as previously described. The skeletal muscle FSR was calculated from the determination of the rate of d 5 -labeled phenylalanine incorporation into the protein and the enrichment of the intracellular pool as the precursor by the following equation Paired t tests were used to compare baseline and treatment data within each group.
Comparisons between the oxandrolone and time control treatment periods were made by unpaired t tests. Patient characteristics are listed in Table 1. The seven control and seven oxandrolone patients were similar in age, sex, weight, percentage TBSA burned, and percentage of third-degree burns. Both groups had delayed presentation to our burn unit of approximately 4 to 6 weeks after injury.
All subjects arrived with open burn wounds that had not received definitive surgical treatment excision of burn and split-thickness skin grafting. The baseline and treatment stable isotope studies were performed at the same times relative to injury in both groups. Nutritional data and energy expenditure are listed in Table 2.
These patients all appeared malnourished, with low body weight in relation to height, temporalis muscle wasting, and exaggerated skeletal prominences. All of them arrived with low albumin, prealbumin, and retinol-binding protein levels. The prealbumin levels in the oxandrolone group were lower than those in the control group, but both groups were profoundly low. After 1 week of continuous enteral feeding, the caloric and protein intakes were the same in both groups, and the levels of the nutritional indices increased.
These values were still far below normal, however, and the oxandrolone group was still lower than the control group. BMR, basal metabolic rate calculated by Harris-Benedict equation. During the second week the treatment time period , dietary intake was again isocaloric and isonitrogenous. At the time of the treatment studies, all nutritional indices had again improved, but they were still below normal. Prealbumin and retinol-binding protein levels were lower in the oxandrolone group. The oxandrolone and control patients showed the same degree of improvement over time, however.
All subjects were hypermetabolic as measured by indirect calorimetry. In each patient, the resting energy expenditure was above the predicted basal metabolic rate from the Harris-Benedict equation.