Effects of the Na+/H+-exchange inhibitor Hoe 642 on intracellular pH, calcium and sodium in isolated rat ventricular myocytes

The inhibitors of the Na+/H+-exchange (NHE1) system Hoe 694 and Hoe 642 possess cardioprotective effects in ischaemia/reperfusion. It is assumed that these effects are due to the prevention of intracellular sodium (Nai) and calcium (Cai) overload. The purpose of the present study was to investigate the effects of Hoe 642 on intracellular pH, Na+ and Ca2+ (pHi, Nai and Cai) in isolated rat ventricular myocytes under anoxic conditions or in cells in which oxidative phosphorylation had been inhibited by 1.5 mmol/l cyanide. In cells which were dually loaded with the fluorescent dyes 2, 7-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and Fura-2, anoxia caused acidification of the cells (from pHi 7.2 to pHi 6.8) and an increase in Cai from about 50 nmol/l to about 1 micromol/l. The decrease in pHi began before the cells underwent hypoxic (rigor) contracture, whereas Cai only began to rise after rigor shortening had taken place. After reoxygenation, pHi returned to its control value and Cai oscillated and then declined to resting levels. It was during this phase that the cells rounded up (hypercontracture). When 10 micromol/l Hoe 642 was present from the beginning of the experiment, pHi and Cai were not significantly different from control experiments. At reoxygenation, pHi did not recover, but Cai oscillated and returned to its resting level. To monitor Nai, the cells were loaded with the dye SBFI. After adding 1.5 mmol/l cyanide or 100 micromol/l ouabain, Nai increased from the initial 8 mmol/l to approximately 16 mmol/l. Hoe 642 or Hoe 694 (10 micromol/l) did not prevent the increase in Nai. In contrast, the blocker of the persistent Na+ current R56865 (10 micromol/l) attenuated the CN--induced rise in Nai. The substance ethylisopropylamiloride was not used because it augmented considerably the intensity of the 380 nm wavelength of the cell's autofluorescence. In conclusion, the specific NHE1 inhibitor Hoe 642 did not attenuate anoxia-induced Cai overload, nor CN--induced Nai and Cai overload. Hoe 642 prevented the recovery of pHi from anoxic acidification. This low pHi maintained after reoxygenation may be cardioprotective. Other possible mechanisms of NHE1 inhibitors, such as prevention of Ca2+ overload in mitochondria, cannot be ruled out. The increase in Nai during anoxia is possibly due to an influx of Na+ via persistent Na+ channels.     

Seasonal variation in light penetration and subsurface chlorophyll-α in southern Lake Michigan observed by a glider

The Cooperative Institute for Great Lakes Research (CIGLR) in collaboration with the Great Lakes Observing System and National Oceanic and Atmospheric Administration, Great Lakes Environmental Research Laboratory (NOAA GLERL) deployed an autonomous underwater glider in southern Lake Michigan several times per year between 2012 and 2019 to collect offshore (>30 m depth) limnological measurements, including temperature, photosynthetically active radiation (beginning during 2015), and chlorophyll-α fluorescence. From these data, we calculated mixed layer depth, several measures of light penetration (diffuse attenuation coefficient, first optical depth, euphotic zone depth), and depth of the subsurface chlorophyll-α maxima. During summer, mean offshore mixed layer depth was typically 10–15 m, K_d for PAR was 0.1–0.17 m^?1, first optical depth was 6–9 m, euphotic zone depth was 35–40 m, and depth of subsurface chlorophyll-α maxima was 30–35 m. We also observed substantial spatial and temporal variation in these values across the basin and within and among seasons. Glider-based observations provide a wider horizontal and vertical perspective than other methods (e.g., ship- and satellite-based observations, buoys, and fixed moorings), and are therefore a valuable, complementary tool for Great Lakes limnology. The set of observations reported here provide seasonal and basin-scale information that may help to identify anomalies useful for future glider-assisted investigation into the role of biophysical processes in Great Lakes limnology and ecology.     

Matching preparatory intervention to coping style: The effects on children's distress in the dental setting

OBJECTIVE: Investigate the effects of matching preparatory interventions to patient's coping styles. METHODS: Participants were 61 children, with a restricted age range of 6 through 9 years old (mean age was 7.9 years), who underwent dental restoration. Participants were randomly assigned to an information intervention, a relaxation intervention, or a control condition. Play and parent-report of sensitization/repression were indices of coping style. The first hypothesis, that play would relate to sensitization/repression, was tested using Pearson correlations. The second hypothesis, that interventions that were congruent with patients' coping styles would be more effective than incongruent interventions, was tested using MANCOVAs. RESULTS: No relation was found between play and coping style. The "congruency hypothesis" was supported for self-reported distress immediately following the intervention. On behavioral distress variables, the interaction between sensitization/repression and condition was contrary to the congruency hypothesis. CONCLUSIONS: Implications for future research and clinical intervention with pediatric populations were discussed.     

IP Squared: Internet Standards and Intellectual Property

Standards-development organizations (SDOs) comprise participants from large and small companies, academia, and the open source community. The participants come with varying backgrounds with regard to copyright and patents in the areas that are being standardized, and the SDOs must deal with these issues in ways that both satisfy the participants (and their employers) and result in useful standards. Each SDO — including the IEEE — has its own intellectual property (IP) policy. This issue, we look at how the IETF handles IP, in an overview cowritten by an attorney who has represented the IETF for some years and the current IETF Chair.     

A parallel algorithm for approximate regularity

Spatial regularity amidst a seemingly chaotic image is often meaningful. Many papers in computational geometry are concerned with detecting some type of regularity via exact solutions to problems in geometric pattern recognition. However, real-world applications often have data that is approximate, and may rely on calculations that are approximate. Thus, it is useful to develop solutions that have an error tolerance.

A solution has recently been presented by Robins et al. [Inform. Process. Lett. 69 (1999) 189–195] to the problem of finding all maximal subsets of an input set in the Euclidean plane that are approximately equally-spaced and approximately collinear. This is a problem that arises in computer vision, military applications, and other areas. The algorithm of Robins et al. is different in several important respects from the optimal algorithm given by Kahng and Robins [Patter Recognition Lett. 12 (1991) 757–764] for the exact version of the problem. The algorithm of Robins et al. seems inherently sequential and runs in O(n^5/2) time, where n is the size of the input set. In this paper, we give parallel solutions to this problem.     

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.