In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model.

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Long lasting in-situ forming implant loaded with raloxifene HCl: An injectable delivery system for treatment of bone injuries.

Bone injury is very serious in elder people or osteoporotic patients. In-situ forming implants (IFI) for bone rebuilding are usually poly-lactic-co-glycolic acid (PLGA)-based, which have a burst release effect. This study aimed to prepare novel liquid lipid-based PLGA-IFI loaded with raloxifene hydrochloride for prolonged non-surgical treatment of bone injuries by applying solvent-induced phase inversion technique. Labrasol® and Maisine® were added to the selected IFI forming long lasting lipid-based IFI (LLL-IFI). The formulations were characterized by analysing their in-vitro drug release, solidification time, injectability, rheological properties, and DSC in addition to their morphological properties. Results revealed that the LLL-IFI composed of 10%w/v PLGA with a lactide to glycolide ratio of 75:25 with ester terminal and 10% Maisine® possessed the most sustained drug release and lowest burst effect, as well as delayed pore formation compared to its counterpart lacking Maisine®. The selected LLL-IFI and PLGA-IFI formulations were tested for their capability to enhance bone regeneration in bone injuries induced in rats. Both formulations succeeded in healing the bones completely with the superiority of LLL-IFI in the formation of well-organized bone structures lacking fibrous tissues. The results suggest that LLL-IFI and PLGA-IFI are innovative approaches for treating critical and non-critical sized bone injuries.

Retinal supplementation augments optogenetic stimulation efficacy in vivo.

OBJECTIVE: Over the last two decades, optical control of neuronal activity in the central nervous system has seen rapid development, demonstrating the utility of optogenetics as both an experimental and therapeutic tool. Conversely, applications of optogenetics in the peripheral nervous system have been relatively constrained by the challenges of temporally variable opsin expression, light penetration and immune attack of non-native opsins. Whilst opsin expression can be increased significantly through high-concentration viral induction, subsequent attack by the immune system causes temporal decay and high variability in electrophysiological response. APPROACH: In this study, we present a method to circumvent the aforementioned challenges by locally supplementing all-trans-retinal (ATR) (via a slow release pellet) to increase tissue photosensitivity in transgenic mice expressing channelrhodopsin 2 (ChR2) in nerves. MAIN RESULTS: In mice supplemented with ATR, we demonstrate enhanced electrophysiological activation and fatigue tolerance in response to optical stimulation for six weeks. SIGNIFICANCE: Local supplementation of ATR enables improved optogenetic stimulation efficacy in peripheral nerves. This method enables greater exploration of neurophysiology and development of clinically-viable optogenetic treatments in the peripheral nervous system.

TRActional DIabetic reTInal detachment surgery with co-adjuvant intravitreal dexamethasONe implant: the TRADITION STUDY.

AIM: Main failure of diabetic tractional retinal detachment (TRD) surgery is the development of proliferative vitreoretinopathy (PVR), causing higher re-detachment rates. We investigated whether the use of dexamethasone (DEX) implant at the end of pars plana vitrectomy (PPV) with silicone oil tamponade might have an impact on these outcomes. DESIGN: Comparative, nonrandomized, retrospective study. PARTICIPANTS: A total of 148 eyes from 148 patients that underwent PPV with silicone oil tamponade for diabetic TRD (with DEX implant, n = 52; without DEX implant, n = 96). METHODS: Consecutive patients' records were reviewed for time between TRD diagnosis and surgery; lens status before surgery and after 6, 12, and 24 months; retina attachment rate after primary PPV; change in postoperative PVR severity; rate of re-detachment at 6, 12, and 24 months; use of IOP lowering treatment after 6, 12, and 24 months; surgery details; intra- and postoperative complications. Correlations between outcome measures, postoperative PVR severity, and re-detachment rates were analyzed. MAIN OUTCOME MEASURES: Change in postoperative PVR severity and retinal re-detachment rates with and without the adjuvant use of DEX implant. RESULTS: Retinal re-detachment rates were significantly higher in the group of patients that did not receive DEX implant [11/96 (11.5%) vs. 0/52 (0%), p = 0.049; 11/84 (12.9%) vs. 4/52 (7.7%), p = 0.007; 14/71 (19.7%) vs. 5/52 (10%) p < 0.001 at 6, 12, and 24 months, respectively]. PVR severity correlated with retinal status at 12 and 24 months (p = 0.018 and p = 0.027, respectively). The difference in PVR severity between the two groups was statistically significant at 6, 12, and 24 months (p < 0.001). CONCLUSIONS: DEX implant at the end of PPV in patients with diabetic TRD improves PVR severity and decreases re-detachment rates. This should be considered as an option in the customized treatment of TRD.

Compound salvia pellet might be more effective and safer for chronic stable angina pectoris compared with nitrates: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic stable angina (CSA) resulted in a considerable burden for both individuals and the society. In this study we aimed to critically evaluate the effectiveness and safety of Compound salvia pellet compared with nitrates in the treatment of Chronic Stable Angina (CSA) pectoris, and to provide more credible evidence for clinical practice. METHODS: A comprehensive and exhaustive search strategy was formulated to identify potential RCTs of compound salvia pellet for CSA in international and Chinese databases from their inception to July 4th, 2018. We also searched the bibliographies of relevant studies. Two reviewers independently assessed the quality of included trials by using Cochrane Risk of Bias Tool. RESULTS: The literature search yielded 1849 citations and 51 RCTs (n = 4732) were included for meta-analysis after titles, abstracts and full text selection according to eligibility criteria. The pooled results suggested that compound salvia pellet was much more effective than nitrates in the improvement of angina symptoms (therapy = 4 weeks, RR = 1.23, 95%CI = [1.17, 1.30], P < .001, I = 0%; therapy = 4 weeks, RR = 1.13, 95%CI = [1.08, 1.17], P < .001, I = 45.6%), and ECG test (therapy = 4 weeks, RR = 1.24, 95%CI [1.14, 1.35], P < .001, I = 51.5%; and therapy > 4 weeks, RR = 1.30, 95%CI[1.20, 1.42], P < .001, I = 36.4%) in CSA. Compared with nitrates, the percentage of patients with adverse events significantly decreased when prescribed with compound salvia pellet (3.2% vs 17.0%). CONCLUSION: Compound salvia pellet might be more effective on the improvement of angina symptoms, ECG test and with few adverse events compared with nitrates. While there are some limitations in this study, which may weaken the results, we believe the findings could provide useful information for stakeholders concerned with outcomes in patients with CSA. More rigorous RCTs with high quality are needed to confirm these findings.

Tobramycin-impregnated calcium sulfate pellets for the treatment of chronic osteomyelitis in children and adolescents.

The aim of this work was to evaluate the outcome and efficacy of treatment in a homogeneous group of skeletally immature patients with chronic osteomyelitis of the long bones managed by a combination of radical debridement and insertion of tobramycin-impregnated calcium sulfate pellets to fill the bone defect in a single-stage procedure. Between 2011 and 2016, 12 skeletally immature patients were treated surgically by the reported technique. Single-stage surgery using tobramycin-impregnated calcium sulfate pellets in association with systemic antibiotic therapy yields satisfactory outcomes in skeletally immature children presenting chronic osteomyelitis by reducing the risk of occurrence of comorbidities, hospital stays, and healthcare costs.

The road to market implantable drug delivery systems: a review on US FDA's regulatory framework and quality control requirements.

The scope of Implantable Drug Delivery Systems (IDDSs) comprehends a variety of sterile therapeutic implements placed inside the body to exert a certain therapeutic action for extended duration. They are classified under different categories from pharmaceutical science and regulatory perspectives. The novelty and variety of IDDSs prevent the application of a uniform regulation for all IDDS products; therefore, sponsors face regulatory challenges to register and market their products. This review investigates pharmaceutical science literature and the United States Food and Drug Administration (US FDA) regulatory guidance to find how any IDDS is classified, regulated, and introduced in the market. The regulatory classification of any IDDS, as a 'drug', 'medical device' or a 'combination product', is the cornerstone in determining the regulatory pathway, which decides the quality control requirements preceding the marketing approval. IDDSs are generally recognized as combination products as they consist of two or more regulated components (drugs, medical devices or biological products) combined prior to use to function as a single entity. Although robust and defined US FDA regulatory pathways exist for each component independent of one another, the regulatory pathways for combination products are less formalized.

Preparation, Characterization and In Vitro / In Vivo Evaluation of Oral Time-Controlled Release Etodolac Pellets.

The objective of this study was to prepare time-controlled release etodolac pellets to facilitate drug administration according to the body's biological rhythm, optimize the drug's desired effects, and minimize adverse effects. The preparation consisted of three laminal layers from center to outside: the core, the swelling layer, and the insoluble polymer membrane. Factors influenced the core and the coating films were investigated in this study. The core pellets formulated with etodolac, lactose, and sodium carboxymethyl starch (CMS-Na) were prepared by extrusion-spheronization and then coated by a fluidized bed coater. Croscarmellose sodium (CC-Na) was selected as the swelling agent, and ethyl cellulose (EC) as the controlled release layer. The prepared pellets were characterized by scanning electron microscopy and evaluated by a dissolution test and a pharmacokinetic study. Compared with commercial available capsules, pharmacokinetics studies in beagle dogs indicated that the prepared pellets release the drug within a short period of time, immediately after a predetermined lag time. A good correlation between in vitro dissolution and in vivo absorption of the pellets was exhibited in the analysis.

Intraocular Dexamethasone Implant as Adjunct to Silicone Oil Tamponade for Proliferative Vitreoretinopathy.

Background Proliferative vitreoretinopathy (PVR) occurs in 10 % of patients with retinal detachment and is characterized by excessive epi-, sub- or intraretinal contraction. Corticosteroids have been shown to counter this contraction. Patients and Methods Retrospective review of 5 patients (3 females, 2 males) with recurrent retinal detachment with stage C PVR. The mean age was 61.2 ± 20.5 years and myopia > - 5.0 dioptres was present in 3 eyes. Patients were treated with 23 g vitrectomy, retinectomy and endolaser, dexamethasone (Ozurdex®) injection under perfluorocarbone and 5500 cs silicone oil tamponade. Results After a total follow-up of 8.8 ± 6.4 months with silicone oil tamponade, the Ozurdex® implant was localised in the macula in 1 case, and in 4 cases behind the iris with a completely attached retina. Preoperative intraocular pressure was 11.0 ± 4.0 mmHg, which remained stable at 7.8 ± 3.5 mmHg at the end of the final follow-up. No localised adverse effects were observed of the implant on the retina or the iris. Conclusions The dexamethasone implant Ozurdex® is well tolerated in conjunction with silicone oil tamponade in eyes with retinal detachment and PVR. The implant may be a potential candidate for the prevention of PVR.

Artificially controlled degradable inorganic nanomaterial for cancer theranostics.

Multifunctional nanomaterials for cancer diagnosis and therapy have recently prompted widespread concern. To avoid nanotoxicity, the development of novel degradable functional materials must be our main focus. In this study, we firstly developed ethylenediaminetetraacetic acid calcium disodium salt (EDTA)- and bovine serum albumin (BSA)-capped Mn3O4 nanoparticles (MONPs-BSA-EDTA) as a novel inorganic nanomaterials for multifunctional imaging-guided photothermal therapy, which can be degraded in a progress-controlled way by artificially introduced ascorbic acid. The degradation products can also be captured and their excretion accelerated. Careful studies suggested that the toxicity of the MONPs-BSA-EDTA and its degradation products is low. The degradation mechanism also suggests a new method of controlled drug release. The development of artificially controlled degradable inorganic nanomaterials also provides a new way to degrade nanomaterials and minimize ion release, which may have potential applications in cancer theranostics without nanotoxicity.

Preclinical assessment of scleral lens as a reservoir-based ocular therapeutic system.

PURPOSE: Bacterial keratitis is a sight threatening infection of the cornea which remains one of the most important potential complications of contact lens use. If the corneal ulcer is small, peripheral with no impending perforation present, intensive monotherapy with fluoroquinolones could be used. Therefore, a study was conducted with the objective to provide pharmacological data of the intra-ocular diffusion after administration of Ofloxacin using a scleral lens reservoir, as well as an evaluation of surface tolerability in rabbits. MATERIALS AND METHODS: Samples of corneas, aqueous humor and vitreous were collected to measure the drug levels of Ofloxacin using High Performance Liquid Chromatography. The corneas were examined by electron microscopy scanning and the eyeballs by light polarizing microscopy in order to evaluate surface tolerability. RESULTS: Ofloxacin levels found in the aqueous humor and cornea were higher than those previously reported. The mean Ofloxacin corneal levels exceeded the MIC (Minimum Inhibitory Concentration) for which 90% of isolates are indicated for all bacteria implicated in keratitis. CONCLUSION: To our knowledge, this is the first preclinical study assessing local tolerance and intra-ocular diffusion of Ofloxacin after administration using a scleral lens reservoir.

Implant-Assisted Intrathecal Magnetic Drug Targeting to Aid in Therapeutic Nanoparticle Localization for Potential Treatment of Central Nervous System Disorders.

There is an ongoing struggle to develop efficient drug delivery and targeting methods within the central nervous system. One technique known as intrathecal drug delivery, involves direct drug infusion into the spinal canal and has become standard practice for treating many central nervous system diseases due to reduced systemic toxicity from the drug bypassing the blood-brain barrier. Although intrathecal drug delivery boasts the advantage of reduced systemic toxicity compared to oral and intravenous drug delivery techniques, current intrathecal delivery protocols lack a means of sufficient drug targeting at specific locations of interest within the central nervous system. We previously proposed the method of intrathecal magnetic drug targeting in order to overcome the limited targeting capabilities of standard intrathecal drug delivery protocols, while simultaneously reducing the systemic toxicity as well as the amount of drug required to produce a therapeutic effect. Building off of our previous work, this paper presents the concept of implant-assisted intrathecal magnetic drug targeting. Ferritic stainless steel implants were incorporated within the subarachnoid space of our in vitro human spine model, and the targeting magnet was placed at a physiological distance away from the model and implant to mimic the distance between the epidermis and spinal canal. Computer simulations were performed to optimize implant design for generating high gradient magnetic fields and to study how these fields may aid in therapeutic nanoparticle localization. Experiments aiming to determine the effects of different magnetically-susceptible implants placed within an external magnetic field on the targeting efficiency of gold-coated magnetite nanoparticles were then performed on our in vitro human spine model. Our results indicate that implant-assisted intrathecal magnetic drug targeting is an excellent supplementary technique to further enhance the targeting capabilities of our previously established method of intrathecal magnetic drug targeting.

The effects of injectable calcium silicate-based composites with the Chinese herb on an osteogenic accelerator in vitro.

We aimed to investigate the physicochemical and biological effects of calcium silicate (CS)-based cements together with the Chinese medicine Xu Duan (XD) after seeding with human adipose-derived stem cells (hADSCs). Here, we fabricated CS-based substrates with different ratios of XD (0%, 5% and 10%) as bioactive and biodegradable biocomposites, subsequent to examining their respective effectiveness for bone repair. The setting time, the injectability, the mechanical properties measured by diametral tensile strength (DTS), the in vitro degradation determined by changes in the weight loss of the composites, the characteristic formation of bone-like apatite, and cell growth as well as osteogenesis protein and bone mineralization were comprehensively evaluated before and after immersion in simulated body fluid (SBF), respectively. At the end of testing, with regard to physicochemical effects, the CS-based substrate mixed with the 10% XD group showed significantly sound mechanical properties, an applicable setting time and injectability and the formation of a dense bone-like apatite layer. In terms of biological effects, the CS-based substrate with the 10% XD group showed a significant development of osteogenic activities with sound cell proliferation and higher alkaline phosphatase (ALP) activity, as well as indicating osteogenic differentiation, greater osteocalcin (OC) protein secretion and clearly calcified tissue mineralization. The present drug-release strategy with CS-based cements may pave the way for future alternative bone repair therapy.

Imparting electroactivity to polycaprolactone fibers with heparin-doped polypyrrole: Modulation of hemocompatibility and inflammatory responses.

Hemocompatibility, anti-inflammation and anti-thrombogenicity of acellular synthetic vascular grafts remains a challenge in biomaterials design. Using electrospun polycaprolactone (PCL) fibers as a template, a coating of polypyrrole (PPy) was successfully polymerized onto the fiber surface. The fibers coated with heparin-doped PPy (PPy-HEP) demonstrated better electroactivity, lower surface resistivity (9-10-fold) and better anti-coagulation response (non-observable plasma recalcification after 30min vs. recalcification at 8-9min) as compared to fibers coated with pristine PPy. Red blood cell compatibility, measured by% hemolysis, was greatly improved on PPy-HEP-coated PCL in comparison to uncoated PCL (3.9±2.1% vs. 22.1±4.1%). PPy-HEP-coated PCL fibers also exhibited higher stiffness values (6.8±0.9MPa vs. 4.2±0.8MPa) as compared to PCL fibers, but similar tensile strengths. It was also observed that the application of a low alternating current led to a 4-fold reduction of platelet activation (as quantitated by CD62p expression) for the PPy-HEP-coated fibers as compared to non-stimulated conditions. In parallel, a reduction in the leukocyte adhesion to both pristine PPy-coated and PPy-HEP-coated fibers was observable with AC stimulation. Overall, a new strategy involving the use of hemocompatible conducting polymers and electrical stimulation to control thrombogenicity and inflammatory responses for synthetic vascular graft designs was demonstrated.

Haloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissue.

Several molecularly imprinted polymers (MIPs) were prepared in the present work, and their binding properties were evaluated in comparison with a nonimprinted polymer (NIP). An optimized MIP was selected and applied for selective extraction and analysis of haloperidol in rabbit brain tissue. A molecularly imprinted solid-phase extraction (MISPE) method was developed for cleanup and preconcentration of haloperidol in brain samples before HPLC-UV analysis. Selectivity of the MISPE procedure was investigated using haloperidol and some structurally different drugs with similar polarity that could exist simultaneously in brain tissue. The extraction and analytical process was calibrated in the range of 0.05-10 ppm. The recovery of haloperidol in this MISPE process was calculated between 79.9 and 90.4%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.008 and 0.05 ppm, respectively. Intraday precision and interday precision values for haloperidol analysis were less than 5.86 and 7.63%, respectively. The MISPE method could effectively extract and concentrate haloperidol from brain tissue in the presence of clozapine and imipramine. Finally, the imprinted polymer was successfully applied for the determination of haloperidol in a real rabbit brain sample after administration of a toxic dose. Therefore, the proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of haloperidol in rabbit brain tissue.

Accelerated healing by composites containing herb epimedium for osteoinductive regeneration.

Porous composites composed of hydroxyapatite (HA), herb epimedium (EP), and chitosan (CS) were used to improve the repair of rabbit bone defects. The in vivo implantation of the HA/CS-EP showed that homogeneous bone formation occurred after 12 weeks' implantation and possessed good osteogenesis. The osteogenic process of the HA/CS-EP group was different from that of the HA/CS group. Direct bone formation of osteoblasts with HA/CS-EP as the matrix could be observed. Compared with the group filled with HA/CS, the group filled with HA/CS-EP showed significant increases in the number of osteoblasts and the bone formation area, and the areas of new bone formation in the HA/CS-EP group after 4 or 12 weeks' implantation reached 33% and 87%, respectively. The novel repair system of HA/CS-EP can induce bone formation, increase osteoblast quantity and improve osteogenesis, for EP can significantly promote the proliferation and activity of osteoblasts in the early stage and accelerate bone remodeling in the later stage. Composites containing EP could be a promising material with multifunctions of osteoinduction, osteoconduction and medication for bone repair, and herb medicine EP could be used as an osteoinduction material for bone tissue engineering.

Surgical and anesthetic considerations in histrelin capsule implantation for the treatment of precocious puberty.

BACKGROUND: Precocious puberty treatment traditionally meant anxiety-provoking monthly depot injections until the advent of the annually implanted histrelin capsule. This study is the first to evaluate the surgical and anesthetic aspects of histrelin implantation for precocious puberty. METHODS: All cases from one surgeon at a tertiary pediatric hospital were reviewed for patient age, anesthetic type, technical difficulties, and complications. RESULTS: From 12/2007 to 3/2013, 114 cases (49% implantations, 25% removals/re-implantations, 25% removals) were performed. Local anesthesia was employed in 100% of non-general anesthesia cases (n=109, 96%), augmented by inhaled N2O in 49%. Five patients (4%) underwent general anesthesia: three neurologically-impaired and two coordinated with scheduled MRIs. Procedural difficulties (n=18, 16%) included implant fracture during removal (n=16/58 removals, 28%). Fracture never occurred during implantation. Three children (3%) suffered complications. One infection was treated with antibiotics, and two implants were removed for systemic allergic reaction. Six children (5%) had unscheduled post-operative checks for pain (n=3, 3%), allergy to elastic dressing (n=2, 2%), or rash (n=1, 1%). Mean charges for general anesthesia were $10,188±1292 versus $528±147 for N2O or local alone (p<0.0001). CONCLUSION: While histrelin implantation is straightforward, removal presents technical challenges. Local anesthesia, with possible N2O supplementation, is well-tolerated and introduces substantial resource and cost savings.

Effects of ractopamine hydrochloride and zilpaterol hydrochloride supplementation on longissimus muscle shear force and sensory attributes of calf-fed Holstein steers.

The effect of ractopamine hydrochloride (RH) and zilpaterol hydrochloride (ZH) on slice shear force (SSF) and sensory characteristics of beef from calf-fed Holstein steers was evaluated. All steers were implanted with a progesterone (100 mg) plus estradiol benzoate (10 mg) implant followed by a terminal trenbolone acetate (200 mg) plus estradiol (40 mg) implant. Steers were blocked by weight into pens (n = 32) randomly assigned to 1 of 4 treatments: control, RH fed at 300 mg·steer(-1)·d(-1) (RH 300) or RH fed at 400 mg·steer(-1)·d(-1)(RH 400) for the final 31 d of finishing, or ZH fed at 6.8 g/t for 21 d with a 5-d withdrawal before harvest. Fourteen carcasses were randomly selected from each pen, and two LM samples (1 per side) were excised and aged either 14 or 21 d before SSF testing. For trained panel evaluation, two steaks were collected from each of 60 low Choice strip loins (20 each from control, RH 300, and ZH treatments) and aged either 14 or 21 d. Steers fed RH and ZH produced steaks with SSF values that were 9% to 25% higher than controls. No difference in SSF was detected between the two levels of RH (P > 0.05). Compared to controls, the probability of steaks aged 14 d failing to meet SSF requirements to be certified tender (SSF < 20 kg) was increased 0.15, 0.17, and 0.26 in steers fed RH 300, RH 400, and ZH, respectively. Compared to controls, the probability of steaks aged 21 d having SSF values >20 kg was increased 0.03, 0.08, and 0.16 in steers fed RH 300, RH 400, and ZH, respectively. Steaks from Select carcasses of steers fed ZH aged 21 d postmortem had double the probability (0.39 vs. 0.17) of having SSF values >20 kg compared to steaks from steers fed either level of RH (P < 0.05). This difference tended to be identical in steaks from Select carcasses 14 d postmortem (0.50 vs. 0.33; P = 0.11); however, no difference was found in low Choice samples at 14 or 21 d postmortem. Trained panelists rated steaks aged 14 d from steers fed ZH lower for overall tenderness and flavor compared to controls (P < 0.05); however, no difference was found between controls and those fed RH 300. Steaks from steers fed ZH aged 21 d were rated lower for overall tenderness and juiciness compared to controls and those from steers fed RH 300 (P < 0.05). This study suggests RH and ZH negatively impact sensory attributes of beef from calf-fed Holstein steers.

Effects of ractopamine hydrochloride and zilpaterol hydrochloride supplementation on carcass cutability of calf-fed Holstein steers.

Effects of ractopamine hydrochloride (RH) and zilpaterol hydrochloride (ZH) on saleable yield of carcass sides from calf-fed Holstein steers were evaluated using steers implanted with a progesterone (100 mg) plus estradiol benzoate (10 mg) implant followed by a terminal trenbolone acetate (200 mg) plus estradiol (40 mg) implant. Steers were blocked by weight into pens (n = 32) randomly assigned to one of four treatments: control, RH fed at 300 mg•steer(-1)/d(-1) (RH 300) or RH fed at 400 mg•steer(-1)/d(-1) (RH 400) the final 31 d of finishing, and ZH fed at 60 to 90 mg•steer(-1)/d(-1) (7.56 g/ton on a 100% DM basis) for 21 d with a 5 d withdrawal before harvest. Eight to nine carcass sides were randomly selected from each pen; carcass sides with excessive hide pulls, fat pulls or bruises were avoided. Cutout data were collected within a commercial facility using plant personnel to fabricate sides at a rate of one every 3 to 4 min into items typically merchandised by the facility. All lean, fat and bone were weighed and summed back to total chilled side weight with a sensitivity of ± 2% to be included in the data set. Compared to controls, ß-agonists increased saleable yield of whole-muscle cuts by 0.61%, 0.86% and 1.95% for RH 300, RH 400 and ZH, respectively (P < 0.05). Percent fat was less in carcasses from the ZH treatment compared to controls (P < 0.05); however, this difference was not observed between RH treatments and controls (P > 0.05). Percent bone was less in the ZH treatment due to increased muscle (P < 0.05). The percent of chilled side weight comprised of trimmings was unchanged between treatments, but on a 100% lean basis, RH 400 and ZH increased trim yields (P < 0.05). Analysis of saleable yield by primal showed a fundamental shift in growth and development. Beta-agonists caused a shift in proportion of saleable yield within individual primals, with a greater portion produced from the hindquarter relative to the forequarter, specifically in those muscles of the round (P < 0.05). Beta-agonists increased saleable yield, but these effects were not constant between all major primals. The cutout value gained by packers as a result of ß-agonist use may be influenced more by reduced fatness and increased absolute weight if musculature is primarily increased in the lower priced cuts of the carcass.

Synthesis of a disulfide cross-linked polygalacturonic acid hydrogel for biomedical applications.

Polygalacturonic acid (PGA) hydrogel cross-linked via disulfide bonds was synthesized using a thiol oxidation reaction. PGA was grafted with cysteine to yield thiolated PGA (denoted PGAcys). Per gram, PGA-conjugated cysteine was 725 ± 77 µmol, and the degree of modification was 16.24 %. A PGAcys hydrogel film was fabricated under physiological conditions, with gel content 91.6 % and water content 43.3 %. The PGAcys hydrogel was used as a drug carrier for rosmarinic acid (RA) (denoted PGAcys/RA) and to prevent postsurgical adhesion. The in vitro dynamic release behavior of RA from the PGAcys hydrogel was analyzed. The profiles showed that 80 % of the total RA was released from the hydrogel within 15 min, followed by zero-order kinetic release. Animal implant studies showed that PGAcys and PGAcys/RA hydrogel films reduced adhesion incidence by over 90 %, significantly higher than did Hyaluronate/Carboxymethylcellulose (analogous Seprafilm™) (42 %). The PGAcys/RA hydrogel film also reduced the early inflammatory reaction.