Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Chemoenzymatic Total Synthesis of Sorbicatechol Structural Analogues and Evaluation of Their Antiviral Potential

Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family.     

Crossing times: Temporal boundary-spanning practices in interorganizational projects

This paper introduces the notion of “temporal boundary spanning” and highlights the key role of project management in resolving temporal tensions among partners participating in interorganizational projects (IOPs). The present study, which is based on data from 93 IOPs undertaken within a major change program, relies on in-depth, semi-structured interviews, observations, and detailed analyses of written documents and procedures from those IOPs. Based on the data, we inductively develop a practice-based theory that identifies three main practices (framing, synchronizing, hyping) used to resolve the central temporal tensions observed in the studied IOPs. In that respect, the paper offers novel insights into the role and practice of project management in IOPs.     

Different bacterial models for in vitro induction of non‐cavitated enamel caries‐like lesions: Microhardness and polarized light miscroscopy analyses

The aim of this study was to compare different bacterial models for in vitro induction of non‐cavitated enamel caries‐like lesions by microhardness and polarized light microscopy analyses. One hundred blocks of bovine enamel were randomly divided into four groups (n = 25) according to the bacterial model for caries induction: (A) Streptococcus mutans, (B) S. mutans and Lactobacillus acidophilus, (C) S. mutans and L. casei, and (D) S. mutans, L. acidophilus, and L. casei. Within each group, the blocks were randomly divided into five subgroups according to the duration of the period of caries induction (4–20 days). The enamel blocks were immersed in cariogenic solution containing the microorganisms, which was changed every 48 h. Groups C and D presented lower surface hardness values (SMH) and higher area of hardness loss (ΔS) after the cariogenic challenge than groups A and B (P < 0.05). As regards lesion depth, under polarized light microscopy, group A presented significantly lower values, and groups C and D the highest values. Group B showed a higher value than group A (P < 0.05). Groups A and B exhibited subsurface caries lesions after all treatment durations, while groups C and D presented erosion‐type lesions with surface softening. The model using S. mutans, whether or not it was associated with L. acidophilus, was less aggressive and may be used for the induction of non‐cavitated enamel caries‐like lesions. The optimal period for inducing caries‐like lesions was 8 days. Microsc. Res. Tech. 78:444–451, 2015. © 2015 Wiley Periodicals, Inc.     

Acylated ascorbate stimulates collagen synthesis in cultured human foreskin fibroblasts at lower doses than does ascorbic acid

Acylated derivatives of ascorbic acid were found to be active in a number of biochemical and physiological processes. In the present study we investigated the effects of 6-O-palmitoyl ascorbate on collagen synthesis by cultured foreskin human fibroblasts. Our observations indicate a marked stimulatory effect on collagen synthesis by 6-O-palmitoyl ascorbate in the concentration range of 5-20 microM, while the synthesis stimulated by ascorbic acid was maximal at concentrations of 20-100 microM. Cells treated with 10 microM palmitoyl ascorbate for 36 h exhibited a production of collagen threefold greater than those in the presence of 10 microM ascorbic acid, and it was about the same as in cells treated with 100 microM ascorbic acid. By 48 h differences were not significant. Acylated ascorbate impaired vitality of the treated fibroblasts at concentrations exceeding 20 microM in media supplemented with 0.5% FCS. However, most of the cytotoxic effect was neutralized by FCS at a concentration of 10%. The resistance of acylated ascorbate against oxidative degradation as well as the role of free radicals in the modulation of collagen synthesis by ascorbic acid and by its derivatives is discussed.     

Homeless youth and their exposure to and involvement in violence while living on the streets

Sick building syndrome is the term given to a heterogeneous constellation of symptoms that affects workers in modern mechanically ventilated office buildings. Although the cause is unknown, there is evidence that the local environment of the work station is an important determinant of symptoms. In this study, investigators examined the effect of a new, individually controlled ventilation system on workers' symptoms. Investigators studied two groups of workers in one mechanically ventilated office building: (1) a control group at whose worksite no intervention was made and (2) an intervention group. The intervention consisted of installation of a device that allowed each worker control over the ventilation supplied to his or her worksite. Just before, and 4 and 16 mo after installation of this device, workers completed self-administered questionnaires regarding occurrence of symptoms. The new ventilation system resulted in higher air velocities, more variable temperatures, and higher concentrations of airborne dust and fungal spores. Four months after installation, workers with the new ventilation system reported fewer symptoms that were (a) work-related (p < .05) and that were work-related and frequent (p < .05); in addition, they reported fewer symptoms that reduced their capacity to work (p < .01). Sixteen months after installation, workers with the new device reported fewer symptoms than at baseline (although not as significantly), and they indicated that the indoor air quality improved their productivity by 11%, compared with a 4% reduction of productivity among the control group of workers (p < .001). Investigators concluded that the new ventilation system, which provided the workers with individual control over ventilation, was associated with important and sustained reduction in symptoms.     

The dynamic transformation of deformed austenite at temperatures above the Ae3

Recent observations regarding the dynamic transformation of deformed austenite at temperatures above the Ae₃ are reviewed. Experimental results obtained on four different steels over the temperature range from 743 to 917 °C and at strains up to ε = 5 are described. It is shown that there is a critical strain for the formation of superequilibrium ferrite and that the volume fraction of transformed ferrite increases with the strain. The structures observed are Widmanstätten in form and appear to have nucleated displacively. The effect of deformation on the Gibbs energy of austenite is estimated by assuming that the austenite continues to work-harden after initiation of the transformation and that its flow stress and dislocation density can be derived from the experimental flow curve by making suitable assumptions about two-phase flow. By further taking into account the inhomogeneity of the dislocation density, Gibbs energy contributions (driving forces) are derived that are sufficient to promote transformation as much as 100 °C above the Ae₃. The C diffusion times required for the dynamic formation of the cementite particles observed are estimated. These range from ～25 to 100 μs and are therefore consistent with the times available during rolling. The Gibbs energy calculations suggest that growth of the Widmanstätten ferrite is followed by C diffusion at the lower carbon contents, while it is accompanied by C diffusion at the higher carbon levels.     

Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case–control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CI_corr) 1.02–3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CI_corr 1.06–3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.