In an effort to control weight gain, much attention has focused on the identification of bioactive peptides from food sources that induce satiety hormone secretion and increase the feeling of fullness. In this study, a screening platform identified a sodium caseinate hydrolysate, LFC25, that significantly increased calcium signalling in the enteroendocrine cell line, STC-1, and as a result increased secretion of the satiety hormone, GLP-1, in a dose-dependent manner. Administration of this hydrolysate to mice reduced the cumulative food intake over an eight hour period. To determine the feasibility of LFC25 as a food ingredient, production was scaled up to 10 L and spray-dried or freeze-dried without loss of bioactivity.

Previously we identified a sodium caseinate (NaCas) hydrolysate, LFC25, which significantly increased secretion of satiety hormone glucagon-like peptide-1 (GLP-1) in vitro and reduced food intake in mice when administered intraperitoneally. This study investigates whether LFC25, administered orally, promotes GLP-1 secretion and/or reduces food intake in vivo. Over an 8-hour period, mice received LFC25 by oral gavage had similar food intake to mice received NaCas. Postprandial blood glucose, plasma active GLP-1, amino acids, insulin and food consumed at the next meal were not significantly different in pigs that consumed LFC25 compared to NaCas in a dairy beverage, at a dosage relevant for human consumption. Simulated in vitro gastro-duodenal digestion of LFC25 revealed a significant reduction in bioactivity. In contrast, the harsh conditions of the upper gut appear to functionalize intact NaCas as a GLP-1 secretagogue. In conclusion, LFC25 will need enteric protection to be used as a food ingredient for satiety.

The low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) is being developed to treat the signs and symptoms of severe osteoarthritis of the knee. This study was a post hoc pooled analysis of 3 randomized placebo-controlled trials of a single intra-articular injection of LMWF-5A, focusing on the subset of patients with severe osteoarthritis of the knee (Kellgren-Lawrence grade 4). Patients were randomized 1:1 to receive a single 4-mL intra-articular knee injection of either LMWF-5A or saline. Safety was assessed as the incidence and severity of adverse events. Efficacy was assessed as the change from baseline to week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index pain (primary outcome), stiffness, and physical function subscores and on patient global assessment scores and was presented as the least squares mean difference and 95% confidence interval. The proportion of responders was defined with the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria for scenario D and examined with Pearson's chi-square test. For 417 patients with severe osteoarthritis of the knee, treatment with LMWF-5A resulted in a significant decrease in pain at 12 weeks compared with saline (mean difference, -0.19; 95% confidence interval, -0.34 to -0.04; P=.016), with improvements in function (mean difference, -0.15; 95% confidence interval, -0.31 to 0.01) and patient global assessment (mean difference, -0.30; 95% confidence interval, -0.49 to -0.12) and higher responder rates (64.25% vs 50.90%, P=.006). No drug-related serious adverse events and no deaths occurred, and the incidence and severity of adverse events were similar across treatment groups. This pooled analysis supports the use of LMWF-5A as a safe therapeutic agent for relief of the signs and symptoms of severe osteoarthritis of the knee. [Orthopedics. 2018; 41(1):e77-e83.].

The hydrolysis of sodium caseinate during heating for up to 120 min at pH 7.0 and 130 degrees C was investigated. The formation of 2% trichloroacetic acid (TCA)-soluble peptides was studied using spectrofluorimetry and high resolution liquid chromatography-mass spectrometry (LC-MS), whereas sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to study hydrolysis of the caseins. LC-MS and spectrofluorimetry showed an increase in 2% TCA-soluble peptides over time, confirming that proteolysis had occurred, whereas SDS-PAGE showed a decrease in band intensity for the main caseins over time. In total, 1023 casein-derived peptides were identified. For eleven of the most abundant peptides, release and breakdown were modelled. Peptide bonds containing Pro, Ser, Asn and/or Asp were preferentially hydrolysed during heating. The production of peptides in this manner may represent a novel alternative to enzymatic hydrolysis strategies. (C) 2015 Elsevier Ltd. All rights reserved.

Osteoarthritis of the knee (OAK) is a common form of arthritis that can lead to substantial pain and disability. This commentary highlights key aspects of the recently published phase 3 A Efficacy and Safety Study of Two Doses of Intra-Articular Injection of Ampion™ in Adults With Pain Due to Osteoarthritis of the Knee (SPRING) study. SPRING (NCT01839331) was a multicenter, randomized, vehicle-controlled, double-blind trial that evaluated the safety and efficacy of the low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) for treatment of pain, measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain scale, in patients with symptomatic OAK (N=329). Patients in this study reflected many characteristics of “real-world” individuals with OAK, with a broad range of disease severity and disability. The most important finding from this study was that treatment with a single intra-articular injection of LMWF-5A led to significant pain reduction in the patients with objective radiographic evidence of severe disease and joint deterioration (Kellgren-Lawrence grade 3; P=0.04 and Kellgren-Lawrence grade 4; P=0.02). The magnitude of pain reduction in the entire cohort treated with LMWF-5A was 42% from baseline and the treatment effect compared with vehicle control (estimated difference in WOMAC pain, −0.25; P=0.004) was also notable, especially relative to a previously reported study of hyaluronic acid, in which only a marginally significant treatment effect was observed (mean difference in WOMAC pain compared with control, −0.15; P=0.047). Significant improvement in physical function observed with LMWF-5A (P=0.04) was also noted and suggests that LMWF-5A may provide therapeutic benefit for those who are limited in the activities of daily living. Intra-articular injection of LMWF-5A was well tolerated, and the adverse event profile was similar to that of control. These results demonstrate significant benefit of LMWF-5A for patients with greatest disability (Kellgren-Lawrence grades 3 and 4) and highest therapeutic need who have limited pharmacologic options for relief of pain associated with OAK.

Colostrum is the initial milk secreted by mammals following parturition, the composition and physicochemical properties of which are highly dynamic and variable. The composition and physicochemical properties of colostrum during the initial post-partum period has not been systematically reviewed for many years, although the topic remains of interest both to milk producers and processors. In this article, the current understanding of the composition of colostrum, i.e. carbohydrates, proteins, growth factors, enzymes, enzyme inhibitors, nucleotides and nucleosides, cytokines, fats, vitamins and minerals, is reviewed. In addition, the physicochemical properties, i.e. pH and buffering capacity, colour, density and specific gravity, osmotic pressure, somatic cell count, properties of casein micelles, ethanol stability and rennet coagulation properties are discussed, as well as the effects of heat-treating colostrum.

Objective: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis.Methods: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1:1:1:1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs).Results: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%).Conclusions: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee.

Introduction Genu recurvatum is a deformity rarely seen in patients receiving total knee arthroplasty. This deformity is defined as hyperextension of the knee greater than 5°. The incidence of recurvatum has been cited in the literature as less than 1%. Purpose The purpose of this study was to report data on 1510 consecutive total knee replacements (TKR) with navigation to demonstrate that the incidence of genu recurvatum is higher than what is cited in the literature. Methods This is a retrospective review that was approved by our health science institutional review board. We reviewed resting, intra-operative alignment of 206 navigated total knee arthroplasty cases with recurvatum. This is data from 4 surgeons who are lower extremity joint replacement physicians. The range of motion (ROM) is measured and recorded by the attending physician during routine physical examination of the lower extremity. Demographic data was used to describe the patient group. The data will include pre-operative, intra-operative and post-operative ROM. The intra-operative data will be captured by the navigation system, this sytem is accurate to 1° and 1mm. The post-operative ROM will be obtained from an office visit. We are interested in the post-operative ROM to demonstrate correction of the recurvatum. Results One thousand five hundred and ten primary TKR were reviewed for this study. Two hundred and six patients (13.6%) had genu recurvatum as measured by the navigation computer. The range of recurvatum was 0.5–30°; mean 5 degrees (STD 4.3°). Sixty six patients had >5 degrees of recurvatum (4.4%). Only 2 patients had recurvatum recorded on their pre-operative office visit. These 2 patients did not have extreme recurvatum, 3° and a few degrees on walking respectively. No patient had recurvatum at the 4 year visit (visit range 3 months – to 4 years). The primary diagnosis for the group was osteoarthritis, 92 %. All cases of recurvatum were treated with under resection of the femur and correction of the coronal plane. All cases were corrected intraoperatively. Conclusion Etiology of recurvatum can be due to bony insufficiency at the anterior tibia, insufficiency at both femoral condyles or laxity of the posterior capsule and ligaments. During surgery this can be addressed by under resection of the femur and undersizing the femoral component to increase the flex space, or soft tissue tightening can be implemented. Our surgical technique aimed to balance hyperextension with reduction of the distal femoral cut. Coronal balance is also important in the management of hyperextension. Current total knee designs lack the extension cam effect and make sagital balancing critical. Recurvatum is difficult to correct after total knee arthroplasty and this issue is important to address at the time of primary surgery. The use of a navigation system helped us appreciate a deformity that is not easily detected during routine examination. This study found that genu recurvatum in patients receiving TKR is significantly higher than what is reported in the literature. This finding has important implications for the management of a small percentage but nonetheless significant number of patients. This deformity is not appreciated in the clinical setting during routine examination.