Inpatient Proton Pump Inhibitor Administration and Hospital-Acquired Clostridium difficile Infection: Evidence and Possible Mechanism

The incidence of Clostridium difficile infection continues to increase globally. Particularly concerning are hospital-acquired cases that attribute significant morbidity, mortality, and expenditures to the health care system. Proton pump inhibitors, which are widely prescribed and generally considered to have minimal adverse effects, have recently come under scrutiny for positive associations with C. difficile infection development. This article will specifically review the current state of evidence demonstrating a positive association between nosocomial proton pump inhibitor administration and the incidence of hospital-acquired C. difficile infection. In addition, the article delivers state-of-the-art knowledge relative to mechanisms by which proton pump inhibitor exposure may propagate the manifestation of C. difficile infection.     

Inhalation device options for the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by chronic respiratory symptoms and airflow limitation, resulting from abnormalities in the airway and/or damage to the alveoli. Primary care physicians manage the healthcare of a large proportion of patients with COPD. In addition to determining the most appropriate medication regimen, which usually includes inhaled bronchodilators with or without inhaled corticosteroids, physicians are charged with optimizing inhalation device selection to facilitate effective drug delivery and patient adherence. The large variety of inhalation devices currently available present numerous challenges for physicians that include: (1) gaining knowledge of and proficiency with operating different device classes; (2) identifying the most appropriate inhalation device for the patient; and (3) providing the necessary education and training for patients on device use. This review provides an overview of the inhalation device types currently available in the United States for delivery of COPD medications, including information on their successful operation and respective advantages and disadvantages, factors to consider in matching a device to an individual patient, the need for device training for patients and physicians, and guidance for improving treatment adherence. Finally, the review will discuss established and novel tools and technology that may aid physicians in improving education and promoting better adherence to therapy.     

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.     

Spray freeze drying for dry powder inhalation of nanoparticles

Formulating nanoparticles for delivery to the deep lung is complex and many techniques fail in terms of nanoparticle stability. Spray freeze drying (SFD) is suggested here for the production of inhalable nanocomposite microcarriers (NCM). Different nanostructures were prepared and characterized including polymeric and lipid nanoparticles. Nanoparticle suspensions were co-sprayed with a suitable cryoprotectant into a cooled, stainless steel spray tower, followed by freeze drying to form a dry powder while equivalent compositions were spray dried (SD) as controls. SFD-NCM possess larger specific surface areas (67–77 m²/g) and lower densities (0.02 g/cm³) than their corresponding SD-NCM. With the exception of NCM of lipid based nanocarriers, SFD produced NCM with a mass median aerodynamic diameter (MMAD) of 3.0 ± 0.5 μm and fine particle fraction (FPF ⩽ 5.2 μm) of 45 ± 1.6% with aerodynamic performances similar to SD-NCM. However, SFD was superior to SD in terms of maintaining the particle size of all the investigated polymeric and lipid nanocarriers following reconstitution (S_f/S_i ratio for SFD ≈ 1 versus >1.5 for SD). The SFD into cooled air proved to be an efficient technique to prepare NCM for pulmonary delivery while maintaining the stability of the nanoparticles.     

坤泰胶囊对大鼠胚胎和胎仔的发育毒性研究

目的 评价SD孕鼠在致畸敏感期（怀孕第6～15天）ig给予坤泰胶囊溶液对SD大鼠的母体毒性、胚胎-胎仔毒性和致畸性。方法 雌性SD大鼠低、中、高剂量组在怀孕第6～15天内分别ig给予2.5、5、10 g/(kg?d) 坤泰胶囊成品粉溶液，对照组给予双蒸水。试验期内每天观察动物的一般情况和临床毒性表现；记录孕鼠的体质量；在怀孕第20天进行剖腹检查，摘取卵巢和子宫，观察黄体数、着床数、胚胎生存及死亡情况、生存胎仔的外观、性别、体质量、骨骼及脏器发育等指标。结果 孕鼠及胚胎、胎仔发育的上述各观察指标未见明显异常，与对照组比较无显著差异。结论 在本实验条件下，坤泰胶囊成品粉未见明显的母体毒性与胚胎和胎儿发育毒性。