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.     

A systematic review of the safety and efficacy of non-operative management in patients with high grade liver injury

IntroductionThe liver is the most frequently damaged organ in blunt abdominal trauma. It is widely accepted that hemodynamically stable patients with low-grade liver trauma should be treated with non-operative management, however there is controversy surrounding its safety and efficacy in high-grade trauma. The purpose of this review is to investigate the role of non-operative management in patients with high-grade liver trauma.MethodsPubMed and reference lists of PubMed articles were searched to find studies that examined the efficacy of non-operative management in high-grade liver injury patients, and compare it to operative management. Non-operative management was considered successful if rescue surgery was avoided. Outcomes considered were success, mortality, and complication rates.ResultsThe electronic search revealed 2662 records, 8 of which met the inclusion criteria. All 8 studies contained results suggesting that non-operative management was safe and effective in hemodynamically stable patients with high-grade liver trauma. By combining the outcomes of the different studies, non-operative management had a high success rate of 92.4% (194/210) in high-grade liver trauma patients, which was near the overall 95.0% non-operative management success rate. Non-operative management also had mortality and complication rates of 4.6% (9/194) and 9.7% (7/72) in high-grade injury patients, respectively, compared to operative management's 17.6% (26/148) and 45.5% (5/11).ConclusionNon-operative management of liver trauma is safe and effective in hemodynamically stable patients with high-grade liver injury. It is associated with significantly lower mortality compared with operative management. More studies are required to evaluate complications of non-operative management in high-grade liver injury.     

Color Stability of Dry Earth Pigmented Maxillofacial Silicone A-2186 Subjected to Microwave Energy Exposure

PURPOSE: The purpose of this study was to measure spectrophotometrically the color stability of pigmented A-2186 silicone maxillofacial elastomer with 10% by volume of titanium white dry earth opacifier before and after exposure to microwave energy over a simulated 1.5-year period of microwave sterilization. Materials AND METHODS: A-2186 silicone elastomer opacified with titanium white dry earth pigment, pigmented with 5 cosmetic dry earth pigment colors [no pigment (control) group (Pc), red (Pr), yellow ochre (Py), burnt sienna (Po), and a mixture of Pr + Py + Po color group (P3)], was used in this study. Each of the 5 experimental groups consisted of 5 specimens. All specimens were placed in a 250 ml glass beaker filled with 150 ml of water (replenished for each microwave exposure). An exposure of 6 minutes was used 18 times (simulating 1.5 years of microwave sterilization with one 6 minute exposure monthly). Reflectance values were measured by spectrophotometer. Three- and two-way analyses of variance with repeated measures were performed for the color difference (DeltaE*) with the factors of group/color/months, and group/months, respectively. Means were compared by Tukey Honest Significant Difference (HSD) multiple range test calculated at the 0.05 level of significance using SPSS. RESULTS: The trained human eye can detect color changes (DeltaE*) greater than 1.0. Most DeltaE* values of the red pigment group at all intervals and the mixed pigment group at 15- and 18- month intervals increased significantly greater than 1.0 (p < 0.001) compared with the control group. Yellow and burnt sienna groups remained the most color stable over time with DeltaE* values below 0.35. CONCLUSIONS: Lack of color stability of red dry earth pigmented A-2186 silicone maxillofacial elastomers was clinically significant after 12-month exposure to microwave energy as compared with yellow, burnt sienna, and opacified A-2186 dry earth pigments.     

替硝唑葡萄糖注射液的稳定性研究

采用反相ＨＰＬＣ法测定替硝唑葡萄糖注射液中替硝唑的含量，用加温加速实验研究该制剂的热稳定动力学。结果表明，替硝唑的热降解反应为一级动力学过程，在５０、６５、８０、９５℃时的降解速度常数分别为５．５８×１０－４、２．６６×１０－３、８．１０×１０－３、２．８２×１０－２ｄ－１，为８．３年，半衰期为３９．５年。     

Atrial Synchronous Ventricular Pacing with a Single Lead: Reliability of Atrial Sensing During Physical Activities, and Long-term Stability of Atrial Sensing

A VDD pacing system with bipolar single-pass leads, were implanted in 36 consecutive patients (average age 72 ± 2years) with high degree atrioventricular block and normal sinus node function. At implant the atrial signal amplitude was 2.6 ± 0.2mV measured by a pacing system analyser (PSA), 1.8 ± 0.1mV measured peak-to-peak from the telemetered calibrated electrogram, and 1.3 ± 0.1mV measured from the sensing threshold. At one month follow-up the peak-to-peak amplitudes (mV) of the telemetered atrial electrograms were not significantly different measured continuously during resting supine with quiet breathing (1.4 ± 0.1), sitting (1.6 ± 0.2). standing (1.5 ± 0.1), arm swinging (1.4 ± 0.2), hyperventilation (1.3 ± 0.1), Vaisalva manoeuvre (1.4 ± 0.1), and treadmill exercise (1.9 ± 0.6). The telemetered atrial electrogram amplitude and the atrial sensing threshold varied between 1.2 ± 0.09mV and 1.8 ± 0.1mV, and between 0.95 ± 0.07mV and 1.3 ± 0.01mV, respectively at 0.5, 1, 3, 6 and 12 months follow-up, but the changes were statistically nonsignificant. The Event Summary showed sensing of 98% to 99% of the atrial events at the different follow-up periods.     

丝裂霉素C化学稳定性的研究

在广泛ＰＨ范围内对丝裂霉素Ｃ的化学稳定性进行了研究，测定不同温度下不同ｐＨ时的速率常数，得到不同ｐＨ时的分解活化能及不同温度下的稳定ｐＨ值。活化能数据在ｐＨ５．５及７．８时出现极大值，而不同温度下的两上最稳定（ｐＨ）ｍ恰恰位于两个ｐＨ范围内。     

Stability of subtilisins and related proteinases (subtilases)

The stability towards thermal and chemical (guanidine hydrochloride, GnHCl) denaturation of six inhibited subtilases (mesentericopeptidase, subtilisins BPN′, Carlsberg and DY, proteinase K and thermitase) has been investigated by kinetic and equilibrium studies. The unfolding processes were monitored by circular dichroic and fluorescence spectroscopy. Experiments in the absence and presence of extraneous calcium in the concentration range 2×10^?3-10^?1 M were performed. The presence of calcium in the weak calcium binding site changes the denaturation drastically. The heat- (or GnHCl-) induced unfolding curves obtained using CD spectroscopy show two independent transitions which seem not to have been resolved before. The presence of Ca²⁺ in the second (third in the case of thermitase) binding site increases the T_m, values by 11-21 °C and the δG_D(H₂O) values obtained from denaturation experiments in GnHCl by 6.7-7.2 kcal/mol when an extraneous Ca²⁺ concentration of 2 × 10^?2 M was used. One interpretation is that the initial step of denaturation in the presence of added calcium is the formation of a partially unfolded intermediate form, retaining a highly ordered structure with 60-85% of the a-helix structure of the native enzyme. This intermediate then unfolds at a temperature considerably higher than that of the same proteinases in the absence of added Ca²⁺. The free energy of stabilization of the intermediates is increased by 1.8-2.8 times in comparison with that for the unfolding reactions of the subtilases with empty Ca2/Ca3 binding sites. A second interpretation is that the two steps in the unfolding curves correspond to enzyme without and with calcium in the weak binding site. Fluorescence experiments confirm the mechanism involving the formation of intermediate states. The results are discussed in relation to the X-ray models of the six subtilases.     

种植义齿修复的医学伦理问题

种植义齿是一项新的修复缺失牙方法，本文从医学伦理学的角度出发，探究种植又齿修复过程中应遵循的医德原则，医师高度的责任心、精湛的医术和正确的口腔宣教是保证种植义齿修复成功的关键。