A Comparison of the Efficacy of Various Antioxidants on the Oxidative Stability of Irradiated Polyethylene

Background

Ultrahigh-molecular-weight polyethylene (UHMWPE) is subjected to radiation crosslinking to form highly crosslinked polyethylene (HXLPE), which has improved wear resistance. First-generation HXLPE was subjected to thermal treatment to reduce or quench free radicals that can induce long-term oxidative degeneration. Most recently, antioxidants have been added to HXLPE to induce oxidative resistance rather than by thermal treatment. However, antioxidants can interfere with the efficiency of radiation crosslinking.

Questions/purposes

We sought to identify (1) which antioxidant from among those tested (vitamin E, β-carotene, butylated hydroxytoluene, or pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate]) causes the least reduction of crosslinking; (2) which promotes the greatest oxidative stability; and (3) which had the lowest ratio of oxidation index to crosslink density.

Methods

Medical-grade polyethylene (PE) resin was blended with 0.1 weight % of the following stabilizers: alpha tocopherol (vitamin E), β-carotene, butylated hydroxytoluene (BHT), and pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate] (a hindered phenol antioxidant [HPAO]). These blends were compression-molded into sheets and subjected to electron beam irradiation to a dose of 100 kGy. Equilibrium swelling experiments were conducted to calculate crosslink density. Each PE was subjected to accelerated aging for a period of 2 weeks and Fourier transform infrared spectroscopy was used to measure the maximum oxidation. Statistical analysis was conducted using analysis of variance with Fisher’s protected least significant difference in which a p value of < 0.05 was used to define a significant difference.

Results

The least reduction of crosslinking in antioxidant-containing HXLPE was observed with HPAO, which had a crosslink density (n = 6) of 0.167 (effect size [ES] = 0.87; 95% confidence interval [CI], 0.162–0.173) mol/dm³ compared with 0.139 (ES = 1.57; 95% CI, 0.132–0.146) mol/dm³ (p = 0.020) for BHT, 0.131 (ES = 1.77; 95% CI, 0.123–0.139) mol/dm³ (p = 0.004) for β-carotene, and 0.130 (ES = 1.79; 95% CI, 0.124–0.136) mol/dm³ (p = 0.003) for vitamin E, whereas pure HXLPE had a crosslink density of 0.203 (95% CI, 0.170–0.235) mol/dm³ (p = 0.005). BHT-PE had an oxidation index of 0.21 (ES = 13.14; 95% CI, 0.19–0.22) followed by HPAO-PE, vitamin E-PE and β-carotene-PE, which had oxidation indices of 0.28 (ES = 9.68; 95% CI, 0.28–0.29), 0.29 (ES = 9.59; 95% CI, 0.27–0.30), and 0.35 (ES = 6.68; 95% CI, 0.34–0.37), respectively (p < 0.001 for all groups). BHT-PE had the lowest ratio of oxidation index to crosslink density of the materials tested (1.49, ES = 1.94; 95% CI, 1.32–1.66) followed by HPAO-PE (1.70, ES = 1.52; 95% CI, 1.61–1.80), vitamin E-PE (2.21, ES = 0.52; 95% CI, 2.05–2.38), and β-carotene-PE (2.69, ES = -0.43; 95% CI, 2.46–2.93) compared with control PE (2.47, 95% CI, 2.07–2.88) with β-carotene (p = 0.208) and vitamin E (p = 0.129) not being different from the control.

Conclusions

BHT-modified HXLPE was found in this study to have the lowest oxidation index as well as the lowest ratio of oxidation index to crosslink density compared with vitamin E, HPAO, and β-carotene-modified HXLPEs. More comprehensive studies are required such as wear testing using joint simulators as well as biocompatibility studies before BHT-modified HXLPE can be considered for clinical use.

Clinical Relevance

BHT is a synthetic antioxidant commonly used in the polymer industry to prevent long-term oxidative degradation and has been approved by the FDA for use in cosmetics and foodstuffs. It may be an attractive potential stabilizer for HXLPE in total joint replacements.     

Ureteric reconstruction for the management of transplant ureteric stricture: a decade of experience from a single centre

This study was conducted to review the outcomes of patients who had undergone surgical repair of a ureteric stricture following renal transplantation. All patients who developed a ureteric stricture and underwent ureteric reconstruction following renal transplantation, between December 2003 and November 2013, were reviewed. One thousand five hundred and sixty renal transplants were performed during the study period. Forty patients required surgical repair of a ureteric stricture (2.5%, 25 male, median age 48 [14–78]). The median time to stricture was 3 [1–149] months. 19 patients were reconstructed by reimplantation to the bladder, 18 utilized a Boari flap, two were a pre‐existing ileal conduit and one was an anastomosis to a native ureter. In one patient, reconstruction was impossible and consequently an extra‐anatomic stent was used. Two patients required re‐operation for restricture and kinking. Median serum creatinine at 12 months following surgery was 148 [84–508] μmol/l. There was no 90‐day mortality. Eleven grafts were lost at the time of this study, a median time of 11 [1–103] months after reconstruction. The incidence of ureteric stricture following renal transplant is low. Surgical reconstruction of the transplant ureter is the optimal treatment and is successful in the majority of patients.     

Influence of hydroxyurea on fetal hemoglobin production in vitro

Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 mumol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 mumol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.     

Dipstick urinalysis findings in children with Plasmodium falciparum in the South Tongu District: A case-control study

Background:

Malaria ranks among the major health and developmental challenges facing some of the poorest countries in tropical and sub-tropical regions across the globe. We determined urinary abnormalities and its relationship with parasite density in children ≤12 years with Plasmodium falciparum infection.

Materials and Methods:

From December 2013 to March 2014, we randomly recruited 116 participants comprising 58 malaria patients (cases) and 58 healthy controls from the Comboni Mission and the Sogakope District Hospitals both in the South Tongu district. Blood was collected for the estimation of hemoglobin and total white blood cells; thick and thin blood films were used for the determination of malaria parasite density. Urine was collected for the measurement of the various biochemical components using the automated urine analyzer. A pretested questionnaire was used to obtain demographic and clinical data.

Results:

Urine protein (P < 0.001), blood (P < 0.001), bilirubin (P < 0.001), urobilinogen (P < 0.001), and ketones (P = 0.001) were significantly higher in individuals with P. falciparum infection than in healthy controls. Proteinuria (P = 0.247; r = 0.155), hematuria (P = 0.142; r = 0.195), bilirubinuria (P = 0.001; r = 0.438), urobilinogenuria (P = 0.876; r = 0.021), and ketonuria (P = 0.136; r = 0.198) were positively correlated with malaria parasite density; however, only bilirubinuria was significantly higher at higher parasitemia.

Conclusion:

Malaria has a significant effect on the chemical composition of urine with bilirubin positively correlated with parasite density. Dipstick urinalysis can be used together with light microscopy in resource-limited malaria-endemic areas to accurately diagnose falciparum malaria infection.     

Pharmacy ethical reasoning: a comparison of Australian pharmacists and interns

International Journal of Clinical Pharmacy - Background Ethical reasoning informs decision making and professional judgement, is guided by codes of ethics and conduct, and requires navigation...