Application of disaccharides alone and in combination,for the improvement of stability and particle properties of spray-freeze dried IgG

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.

Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.

Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.

Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules.     

Sarcopenia in cirrhosis: from pathogenesis to interventions

Journal of Gastroenterology - Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation....     

The rat brachial plexus and its terminal branches: An experimental model for the study of peripheral nerve regeneration

Despite the introduction of microsurgical techniques into clinical practice, the results of surgical procedures involving the brachial plexus and peripheral nerves are still far from spectacular. We therefore studied the rat brachial plexus and its terminal branches in 203 rats. Detailed anatomic and morphologic analyses of the biceps brachii and musculocutaneous nerve, finger flexors, flexor carpi radialis, and the median nerve were performed. Various sources of conventional and vascularized nerve grafts were explored. After musculocutaneous nerve section or median nerve section, there were no articular contractures or automutilations, which constitutes an advantage for these experimental models over the sciatic nerve model. The brachial plexus and its terminal branches provide a good experimental model which can be used to assess the development and normal control of muscle function, examine the mechanisms underlying functional recovery, and test the effects of treatments to enhance recovery. © 1995 Wiley-Liss, Inc.     

Monte Carlo assessment of soil moisture effect on high-energy thermal neutron capture gamma-ray by 14N.

Among many conventional techniques, nuclear techniques have shown to be faster, more reliable, and more effective in detecting explosives. In the present work, neutrons from a 5 Ci Am-Be neutron source being in water tank are captured by elements of soil and landmine (TNT), namely (14)N, H, C, and O. The prompt capture gamma-ray spectrum taken by a NaI (Tl) scintillation detector indicates the characteristic photo peaks of the elements in soil and landmine. In the high-energy region of the gamma-ray spectrum, besides 10.829 MeV of (15)N, single escape (SE) and double escape (DE) peaks are unmistakable photo peaks, which make the detection of concealed explosive possible. The soil has the property of moderating neutrons as well as diffusing the thermal neutron flux. Among many elements in soil, silicon is more abundant and (29)Si emits 10.607 MeV prompt capture gamma-ray, which makes 10.829 MeV detection difficult. The Monte Carlo simulation was used to adjust source-target-detector distances and soil moisture content to yield the best result. Therefore, we applied MCNP4C for configuration very close to reality of a hidden landmine in soil.     

Comparison of the detection of subtle changes in myocardial regional systolic function using qualitative and semi-quantitative techniques.

PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall thickening for the assessment of subtle changes in myocardial systolic function using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a significant coronary artery stenosis and in 2 controls on a 1.5T scanner. Qualitative results were obtained using a numerical scoring system; quantitative analysis was performed using a semi-automatic segmentation program. The techniques were matched and compared using Spearman correlations. RESULTS: All correlations in the experimental group revealed significant but weak to moderate relationships between the qualitative and quantitative results (e.g., at-risk tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each identifying changes in regional function that ensued following creation of the stenosis. Intra-observer variability was reasonable in both methods when repeat analysis on a subset of the data was performed, with both techniques showing a significant correlation between the repeated measurements (quantitative - rho = 0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods were able to detect very limited wall motion abnormalities present in the canines with significant stenosis and either method gives comparable results.     

Abdominal wall reconstruction after open management of the septic abdomen

The increasing popularity of open management of the septic abdomen has generated a challenge that the surgeon is forced to face more frequently. The typical presentation is that of a patient with a full-thickness abdominal wall defect occurring after a protracted, severe illness. The various methods of reconstruction of the abdominal wall are reviewed and evaluated. The reconstruction should only be attempted once intra-abdominal sepsis is controlled, re-exploration of the peritoneal cavity is no longer necessary and organ support is discontinued. Although various methods of reconstruction are described, the recommended technique consists of either medial advancement of the rectus abdominis muscle or direct application of split-thickness skin grafts. Mid-line abdominal defects may also be repaired with tensor fasciae latae or rectus femoris flaps.     

Possible venous air embolism during open eye surgery in a child

PURPOSE: Although venous air embolism is a well recognized complication within most surgical subspecialties, it has only been reported recently during eye surgery in one adult, and never before in a child. We describe the case of a 17-month-old boy who sustained a possible air embolism during repair of an open trauma of his right eye. CLINICAL FEATURES: A vitrectomy through the pars plana with air-fluid exchange of the posterior chamber was performed under general anesthesia to remove a foreign body which had impaled the optic nerve. A few minutes after removal of the foreign body, a notable decrease in end-tidal CO(2), oxygen saturation and arterial blood pressure occurred, requiring administration of a high inspired oxygen fraction and vasopressors. Venous air embolism was strongly suspected after other causes of a decrease of end-tidal CO(2) and hypoxemia had been excluded. An arterial blood gas confirmed hypoxemia and respiratory acidosis. CONCLUSION: Although venous air embolism is a rare complication of eye surgery, it should nevertheless be considered as a possible complication during air-fluid exchange vitrectomy in children.     

Glycosaminoglycan mimetics (RGTA) modulate adult skeletal muscle satellite cell proliferation in vitro

Confocal Raman microspectroscopy (CRM) provides an important and novel means of analyzing the chemical composition of the adhesive/dentin (a/d) interface. The purpose of this study was to develop a method for quantitative determination of the degree of adhesive penetration at the a/d interface using CRM. Three commercial dentin adhesive systems [Scotchbond Multipurpose Plus (SBMP+), Single Bond (SB), and Primer Bond NT (PBNT)] based on the total etch and "wet" bonding technique were examined in this study. Human dentin specimens treated with these adhesives were analyzed with CRM mapping across the a/d interface. Also, Raman spectra were collected on model mixtures of adhesive and type I collagen, and the ratios of the relative intensities of the Raman bands corresponding to adhesive and collagen were used for the construction of calibration curves. By comparing the Raman band ratios of interface specimens to the calibration curves, the percent of adhesive as a function of spatial position across the a/d interface was determined. The results show that there is a gradual decrease in penetration as a function of position for all three adhesive systems while the adhesive concentration gradient decreases in the order of SBMP+ > SB > PBNT. These differences in penetration of the three adhesives at the a/d interface also are discussed relative to the composition and phase segregation in adhesives. Additionally, our results indicate that confocal Raman microspectroscopy is a reliable in situ analytical technique for simple and rapid quantitative determination of adhesive penetration at its interface with prepared dentin.