Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model.

BACKGROUND: Postoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model. MATERIAL AND METHODS: Laparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 µg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel. RESULTS: Treatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation. CONCLUSIONS: Keratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.

Halofuginone- and chitosan-coated amnion membranes demonstrate improved abdominal adhesion prevention.

Our objective was to determine whether coating the amniotic membrane with halofuginone, a type 1 collagen synthase inhibitor, with or without the hemostasis-inducing substance chitosan, reduced the number and severity of adhesions in the rat uterine horn injury model. Sixty retired breeder Sprague-Dawley rats underwent midline laparotomy and a zone of ischemia was created in the left uterine horn of each animal. Rats were randomized to one of six treatment groups: (1) untreated control, (2) oxidized regenerated cellulose (Interceed®) (ORC), (3) plain amnion, (4) amnion coated on both sides with 0.5% solution of halofuginone (HAH), (5) amnion coated on one side with 0.5% halofuginone and on the other side with chitosan (CAH), or (6) amnion coated on both sides with chitosan (CAC). The zone of ischemia in each left uterine horn was wrapped in each treatment. Rats were sacrificed 2 weeks after laparotomy, and adhesions were counted and scored for severity. Data were analyzed using Chi square and a p < 0.05 was considered significant. Our results showed that there were no differences in the percentage of animals with adhesions in the untreated, ORC, plain amnion, or CAC groups. No adhesions formed in any animal in the HAH group and only 14% of the animals developed adhesions to the uterine horn in the CAH group (p < 0.05). The percentage of animals with moderate and severe adhesions did not differ between untreated controls and the ORC groups, but were significantly reduced in all four of the amnion groups: plain amnion, HAH, CAH, and CAC (p < 0.05). Amnion coated with halofuginone alone or in combination with chitosan reduced the percentage of animals with adhesions, as well as the percentage of animals with moderate and severe adhesions compared to untreated controls and the ORC group in the rat uterine horn injury model. Amnion alone or coated with chitosan reduced the percentage of rats with moderate and severe adhesions, but not the percentage of rats with adhesions of any type compared to both untreated controls and the ORC group in the rat uterine horn injury model.

Multifactorial preoperative predictors for postcesarean section pain and analgesic requirement.

BACKGROUND: The study aimed to determine predictive factors for postcesarean pain and analgesia using an assessment of pain threshold and suprathreshold thermal stimuli as well as degree of somatization and anxiety. METHODS: Thirty-four healthy parturients scheduled for cesarean delivery under subarachnoid anesthesia were enrolled. Preoperative thermal pain threshold, intensity, and unpleasantness to heat stimuli applied to arm and lower back, State Trait Anxiety Inventory, and patient expectation for postoperative pain and need for analgesia were assessed. After surgery, overall, resting, and movement pain and analgesic consumption were recorded. Prediction of pain and analgesic use outcomes was made by principal component factor analysis, followed by stepwise linear regression. RESULTS: Resting pain was predicted by two factors, thermal pain and unpleasantness and patient expectation (r2 = 0.26, P < 0.01), evoked pain by thermal pain threshold in the back (r2= 0.20, P < 0.009), composite pain by thermal pain and unpleasantness and preoperative blood pressure (r2 = 0.28, P < 0.008), intraoperative analgesic need by preexisting pain (r2 = 0.22, P < 0.006), recovery room analgesia by thermal pain threshold and State Trait Anxiety Inventory (r2 = 0.27, P < 0.01), and total analgesic need by State Trait Anxiety Inventory (r2 = 0.22, P < 0.01). These models predicted the upper twentieth percentile of composite pain scores and analgesic requirement with sensitivity of 0.71 to 0.80 and specificity of 0.76 to 0.80. CONCLUSIONS: The authors' results suggest a meaningful combination of preoperative patient responses from physical and psychological tests yields a valid multifactorial predictive model for postoperative pain and analgesic requirement with significant improvements over individual predictive variables.

Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study.

OBJECTIVE: To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms (hot flashes and night sweats) in peri- and postmenopausal women. DESIGN: A double-masked, randomized, controlled, clinical trial was conducted. A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were randomized into one of three groups. In all groups, participants consumed a daily supplement containing 25 g of soy protein and were randomly assigned to one of three groups: (a) isoflavone extracted soy protein (control), (b) soy protein with a medium dose of isoflavones (42 mg/day), or (c) soy protein with a higher dose of isoflavones (58 mg/day). The primary outcome measure in this trial was change in reported vasomotor symptoms. RESULTS: A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups. No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone, middle isoflavone, or control groups. The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy. CONCLUSIONS: These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women.