Isothermal Microcalorimetry of Pressurized Systems I: A Rapid Method to Evaluate Pressurized Metered Dose Inhaler Formulations

Purpose

The techniques available to study formulation stability in pressurized metered dose inhalers (pMDIs) are limited, due to the challenging conditions of working with high pressure propellants. Isothermal microcalorimetry is a valuable tool used to screen and aid in formulation development of solid and solution drug formulations; however there are currently no available methods to evaluate pMDIs. In this paper, we have developed a method that allows measurement of such pressurized systems.

Methods

Samples were prepared by cold filling ampoules with propellant (HFA 134a) and drugs of interest. Ampoule caps were fitted with a specific O-ring, coated with paraffin and pre-conditioned prior to measurement. Samples were equilibrated at 25°C, placed in a Thermal Activity Monitor III (TAM III) system and measured isothermally at 25°C for a period of at least 24 h.

Results

Using well-defined procedures and ampoule preparation techniques we were able to safely contain the volatile propellant and acquire a stable measurement baseline. We were able to rapidly determine, within 6 h, the physical stability of amorphous and crystalline drug forms of beclomethasone dipropionate and formoterol fumarate dihydrate when formulated with HFA 134a.

Conclusions

Isothermal microcalorimetry in pressurized HFA propellant systems was shown to be a rapid screening tool to evaluate pMDI formulation physical stability. This method can potentially be applied to study pMDI formulation factors to expedite product development.     

经食道超声在缺血性卒中疾病中的应用

目的评估主动脉内膜厚度与腔隙性脑梗塞和非腔隙性脑梗塞的关系。方法选取59例缺血性卒中患者,使用食道超声心动图（TEE）这一技术检测梗塞面积的大小。结果主动脉弓内膜厚度与缺血性卒中的种类有关,腔隙性脑梗塞主动脉弓粥样硬化的发生率是46．7％,非腔隙性脑梗塞主动脉弓粥样硬化的发病率为88．6％。结论TEE检查可以清晰的看见主动脉弓内膜厚度及斑块形成情况,对于缺血性卒中病人的病因的诊断可能衍生出新的临床证据,并对未来治疗提供最佳治疗方案。     

Comparative Investigation of the Efficacy of Three Different Adsorbents against OTA-Induced Toxicity in Broiler Chickens

The aim of our study was to determine the efficacy of three different adsorbents, inorganic (modified zeolite), organic (esterified glucomannans) and mixed (inorganic and organic components, with the addition of enzymes), in protecting broilers from the toxic effects of ochratoxin A in feed. Broilers were fed diets containing 2 mg/kg of ochratoxin A (OTA) and supplemented with adsorbents at the recommended concentration of 2 g/kg for 21 days. The presence of OTA led to a notable reduction in body weight, lower weight gain, increased feed conversion and induced histopathological changes in the liver and kidneys. The presence of inorganic, organic and mixed adsorbents in contaminated feed only partially reduced the negative effects of OTA on the broiler performances. Broilers that were fed with adsorbent-supplemented feed reached higher body weight (17.96%, 19.09% and 13.59%), compared to the group that received only OTA. The presence of adsorbents partially alleviated the reduction in feed consumption (22.68%, 12.91% and 10.59%), and a similar effect was observed with feed conversion. The applied adsorbents have also reduced the intensity of histopathological changes caused by OTA; however, they were not able to prevent their onset. After the withdrawal of the toxin and adsorbents from the feed (21–42 days), all previously observed disturbances in broilers were reduced, but more remarkably in broilers fed with adsorbents.     

快速康复外科护理对胸腔镜肺段切除术患者术后恢复与护理满意度的影响分析

目的 探讨快速康复外科（FTS）护理对胸腔镜肺段切除术患者术后恢复的影响。方法于2016年1月—2017年1月,选取复旦大学附属华山医院胸外科拟行胸腔镜肺段切除手术的患者126例为研究对象。采用随机数表法分为观察组（n=63）和对照组（n=63）。对照组采用传统的胸外科围手术期护理,观察组患者在围手术期给予FTS护理,比较两组患者术后恢复指标、并发症发生率、术后7d的世界卫生组织生存质量测定简表（WHOQOL-BREF）评分以及出院时患者的护理满意度。结果 观察组术后胸腔引流管放置时间、首次排便时间、术后住院天数与并发症的总发生率显著低于对照组,差异具有统计学意义（P＜0.05）。观察组术后7d WHOQOL-BREF量表的生理、心理、社会关系领域评分及总分显著高于对照组,护理满意度显著优于对照组,差异具有统计学意义（P＜0.05）。结论 FTS护理在胸腔镜肺段切除术的围手术期中的应用效果令人满意,能显著促进术后康复,减少术后并发症的发生风险,提高术后生活质量与护理满意度,值得临床推广应用。     

Chemoembolization in hepatocellular carcinoma: multivariate analysis of survival prognostic factors after the first session

AIM: The aim of the study was to determine whether simple routine parameters evaluating the first session of transarterial chemoembolization (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, and post-embolization syndrome) can predict survival of patients treated for hepatocellular carcinoma. METHODS: Seventy-two patients treated with transarterial chemoembolization and evaluated one month after the first sessions with CT scan were included. Transarterial chemoembolization session included hepatic arteriography, lipiodol and doxorubicin (50 mg) emulsion injection, followed by gelatin sponge embolization. The following variables were studied in univariate and multivariate analysis: 6 recorded at the first session (age, cirrhosis etiology, Child-Pugh class, tumor number, largest lesion size, and alpha-fetoprotein concentration), and 5 recorded after the first session (variation in alfa-fetoprotein concentration, tumor lipiodol uptake, post-embolization syndrome, mean interval between each session, and associated treatment). RESULTS: Mean follow-up was 22.7 months (4-106). Mean survival was 30.4 months (95% CI: 23. 3-37.5). Actuarial survival at 1, 2, 3 and 5 years was respectively 65.5%, 44%, 29.5%, and 18%. The only independent prognostic factors in multivariate analysis were the Child Pugh class and the mean interval between sessions (P<0.001 and<0.01 respectively). None of our criteria evaluating the first TACE session significantly influenced survival. CONCLUSION: The 3 parameters (variation in alpha-fetoprotein concentration, tumor lipiodol uptake and post-embolization syndrome) after the first transarterial chemoembolization did not predict survival. They could not be used to determine which patient could benefit from repeated transarterial chemoembolization sessions.     

Effects of diet composition on glucose tolerance and plasma lipids of non insulin-dependent diabetics

Summary The possible influence of qualitative dietary changes on carbohydrate tolerance and plasma lipid levels of non insulin-dependent diabetics was studied in 5 maturity-onset diabetics of normal weight who remained stabilized with 5 to 10 mg glibenclamide. Each patient was submitted to 4 isocaloric qualitatively different diets: standard, high carbohydrate, high fat, and high protein. Each diet was administered for 30 consecutive days in random order. Apart from assessing metabolic control, an oral glucose tolerance test (40 g/m² body surface area) was performed in the morning, at the end of each period. Blood was collected at 0, 60, 120, and 180 min after starting glucose ingestion, for blood glucose and plasma FFA determinations. Fasting total lipids, triglycerides, lipoalbumins, and α- and β-lipoproteins, and 24-h urinary urea were also investigated. The findings did not disclose any differences in carbohydrate tolerance after the various diets. The drop in FFA levels following an oral glucose load was greatest after the high protein diet. Fasting total lipids were lowest after the high fat and high protein diets. Triglycerides fell after the high fat diet. The remaining parameters showed less significant variations. Although no differences were observed in carbohydrate tolerance, the conclusion is that relative carbohydrate restriction together with sufficient protein supply might be most beneficial for non insulin-dependent diabetics.     

Measurable impact of acupuncture on mucosal swelling of inferior turbinates: a prospective,randomized, controlled study

Conclusions: Sham acupuncture turned out to be more effective than expected. The effect of acupuncture cannot be assessed by optical rhinometry (ORM). Objectives: In most cases nasal congestion is caused by hypertrophy of the inferior turbinate as a result of allergic and chronic rhinitis. Topical decongestants cause severe side effects. As a consequence, there is an increasing demand for alternative treatment options such as traditional Chinese medicine (TCM). Methods: A total of 25 patients with nasal congestion due to hypertrophic inferior turbinate were recruited. The mucosal swelling status of the inferior turbinate was assessed by continuous ORM for 20 min. Patients were asked to score the severity of their nasal congestion on a visual analogue scale (VAS) before and 10 and 20 min after acupuncture. Specific verum acupuncture points related to nasal congestion were tested against non-specific control sham acupuncture points. Results: Sham acupuncture improved VAS scores, whereas ORM measured an increase in nasal swelling. The ORM revealed a quicker onset of the effect of verum acupuncture on the nasal blood flow. Also, verum acupuncture reaches its maximum effect in a shorter time period, so that the net reaction time was much shorter. However, ORM could not prove a decongestant effect of verum acupuncture on inferior turbinate.     

A bibliometric analysis of toxicology research productivity in Middle Eastern Arab countries during a 10-year period (2003–2012)

Background

The key to universal coverage in tuberculosis (TB) management lies in community participation and empowerment of the population. Social infrastructure development generates social capital and addresses the crucial social determinants of TB, thereby improving program performance. Recently, there has been renewed interest in the concept of social infrastructure development for TB control in developing countries. This study aims to revive this concept and highlight the fact that documentation on ways to operationalize urban TB control is required from a holistic development perspective. Further, it explains how development of social infrastructure impacts health and development outcomes, especially with respect to TB in urban settings.

Methods

A wide range of published Government records pertaining to social development parameters and TB program surveillance, between 2001 and 2011 in Delhi, were studied. Social infrastructure development parameters like human development index along with other indicators reflecting patient profile and habitation in urban settings were selected as social determinants of TB. These include adult literacy rates, per capita income, net migration rates, percentage growth in slum population, and percentage of urban population living in one-room dwelling units. The impact of the Revised National Tuberculosis Control Program on TB incidence was assessed as an annual decline in new TB cases notified under the program. Univariate linear regression was employed to examine the interrelationship between social development parameters and TB program outcomes.

Results

The decade saw a significant growth in most of the social development parameters in the State. TB program performance showed 46% increment in lives saved among all types of TB cases per 100,000 population. The 7% reduction in new TB case notifications from the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases per 100,000 population. Except per capita income, literacy, and net migration rates, other social determinants showed significant correlation with decline in new TB cases per 100,000 population.

Conclusions

Social infrastructure development leads to social capital generation which engenders positive growth in TB program outcomes. Strategies which promote social infrastructure development should find adequate weightage in the overall policy framework for urban TB control in developing countries.