Effect of HFA-flunisolide on peripheral lung inflammation in asthma

BACKGROUND: New hydrofluoroalkane (HFA) formulations of glucocorticoids have been shown to effectively control asthma. HFA glucocorticoids are deposited across all sizes of airways, including the small ones. However, it is not clear whether they can suppress peripheral airway inflammation. OBJECTIVE: We sought to determine whether HFA-flunisolide could suppress peripheral inflammation in asthma. METHODS: Twelve patients with mild to moderate asthma received HFA-flunisolide for 6 weeks. Transbronchial and endobronchial biopsy specimens were obtained before and after treatment, and spirometry was performed. Changes in inflammatory cells (eosinophils, neutrophils, lymphocytes, macrophages, basophils) and IL-5 and eotaxin were measured by using immunocytochemistry and in situ hybridization. RESULTS: Lung function significantly improved after treatment (P <.05). HFA-flunisolide significantly reduced eosinophils, IL-5, and eotaxin in both peripheral and central airways (P <.01). Neutrophils significantly increased after treatment in peripheral and central airways (P <.05). The numbers of lymphocytes remained unchanged. CONCLUSIONS: These results show that HFA-flunisolide effectively suppressed eosinophilic inflammation in peripheral and central airways. These changes were accompanied by improvement in lung function.     

The effects of midazolam and ketamine on D-tubocurarine-induced twitch depression in septic rat diaphragm

The aim of this study was to elucidate the effects of midazolam and ketamine on neuromuscular blockade induced by non-depolarizing muscle relaxants (NDMRs) under the condition of sepsis induced by panperitonitis. A CLP operation (laparotomy, cecal ligation, and puncture of the cecum; septic group) or sham laparotomy (sham group) was performed on rats under O2-isoflurane anesthesia. At 18 hours after the operation, isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect or direct stimulation at 0.1 Hz were measured. Midazolam enhanced the dTc (1 microM)-induced twitch depression (p < 0.05) at a high concentration (10 microM) in the septic group but not in the sham group. Ketamine enhanced the dTc (1 microM)-induced twitch depression in the sham group (p < 0.01) but not in the septic group. Midazolam and ketamine had no effect on directly elicited twitch tensions in either group. The results indicate that sepsis facilitates the midazolam-induced enhancement of the neuromuscular blocking effect of dTc but, conversely, inhibits the ketamine-induced enhancement. Sepsis elicits manifold alterations in the influence of intravenous anesthetics and sedatives on NDMR-induced neuromuscular blockade.     

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

In vitro synergistic activity between meropenem and other beta-lactams against methicillin-resistantStaphylococcus aureus

The in vitro activity of meropenem, a carbapenem antibiotic, combined with eight other -lactams against methicillin-resistantStaphylococcus aureus (MRSA) was tested. The MICs of these antibiotics alone ranged from 12.5 to 1,600 µg/ml for the 25 clinical isolates of MRSA studied. All combinations with meropenem exhibited marked synergy as determined by the checkerboard method. The MICs in combinations of meropenem with other -lactams were reduced to 1/4 – 1/64 those of the antibiotics alone. No antagonism was observed for any of the combinations of meropenem with other -lactams. Synergism between meropenem and cefpiramide was the highest among the combinations tested, the geometric mean of the fractional inhibitory concentration index for this combination being 0.237. This combination also demonstrated strong bactericidal activity, the MBCs decreasing to 1/16 – 1/64 of those for the agents alone. In terms of the fractional inhibitory concentration index, this was the most effective combination against MRSA highly resistant to meropenem alone with synergism for 85 % (81/95) of the strains. In addition, synergism of imipenem with cephalosporins against MRSA was demonstrated. The affinity of meropenem and cefpiramide for MRSA penicillin-binding protein (PBP) 2 was very low, and the combination of both antibiotics showed an additive increase in affinity for this protein, but not a synergistic increase. Thus, the mechanism of synergism did not seem to be related to affinity for PBP2. It is possible that there is another factor besides PBP2 which increases the resistance of MRSA and that the combinations inhibit the unknown factor.     

Effect of electrolyzed water on wound healing

Electrolyzed water accelerated the healing of full-thickness cutaneous wounds in rats, but only anode chamber water (acid pH or neutralized) was effective. Hypochlorous acid (HOCl), also produced by electrolysis, was ineffective, suggesting that these types of electrolyzed water enhance wound healing by a mechanism unrelated to the well-known antibacterial action of HOCl. One possibility is that reactive oxygen species, shown to be electron spin resonance spectra present in anode chamber water, might trigger early wound healing through fibroblast migration and proliferation.     

Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial

Indian Journal of Pediatrics - To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean...     

Experimental Tests and Numerical Simulations on the Ballistic Impact Response of a Highly Inhomogeneous Aluminium Foam

A sandwich structure is a composite material consisting of thin skins encapsulating a cellular core. Such structures have proven to be excellent energy absorbents and are frequently found in various types of protection. Even so, few studies exist in the open literature on the response of the core material itself under extreme loadings such as blast and impact. Since a blast load is usually accompanied by numerous fragments, it is important to understand and be able to predict the ballistic impact resistance of the often highly inhomogeneous cellular core materials in design. In this study, the ballistic impact response of an aluminium foam with a complex cell structure has been investigated both experimentally and numerically. First, an extensive material test program involving compression tests on cubic specimens loaded in the thickness direction of the foam was carried out to reveal the mechanical properties of the material. In addition, several of the specimens were scanned before testing using X-ray Micro Computed Tomography (XRMCT) to map the multi-scale topology and morphology of the material. These data were later analysed to extract density-variation plots in many different material orientations. Second, ballistic impact tests were conducted using a gas gun where rigid spheres were launched towards aluminium foam plates, and the ballistic limit velocity and curve of the foam material were established. Finally, numerical simulations of both the material tests and the ballistic impact tests were carried out using LS-DYNA and different modelling approaches based on the XRMCT data. It will be shown that, independent of the modelling strategy applied, good agreement between the experimental impact tests and the numerical predictions can be obtained. However, XRMCT data are important if the final goal is to numerically optimise and improve the behaviour of inhomogeneous foams with respect to energy absorption, thermal isolation, or similar properties.