Structural and functional diversity of connexin genes in the mouse and human genome

Gap junctions are clustered channels between contacting cells through which direct intercellular communication via diffusion of ions and metabolites can occur. Two hemichannels, each built up of six connexin protein subunits in the plasma membrane of adjacent cells, can dock to each other to form conduits between cells. We have recently screened mouse and human genomic data bases and have found 19 connexin (Cx) genes in the mouse genome and 20 connexin genes in the human genome. One mouse connexin gene and two human connexin genes do not appear to have orthologs in the other genome. With three exceptions, the characterized connexin genes comprise two exons whereby the complete reading frame is located on the second exon. Targeted ablation of eleven mouse connexin genes revealed basic insights into the functional diversity of the connexin gene family. In addition, the phenotypes of human genetic disorders caused by mutated connexin genes further complement our understanding of connexin functions in the human organism. In this review we compare currently identified connexin genes in both the mouse and human genome and discuss the functions of gap junctions deduced from targeted mouse mutants and human genetic disorders.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Spatial Assessment of Erosion and its Impact on Soil Fertility in the Tajik Foothills

Efficient planning of soil conservation measures requires, first, to understand the impact of soil erosion on soil fertility with regard to local land cover classes; and second, to identify hot spots of soil erosion and bright spots of soil conservation in a spatially explicit manner. Soil organic carbon (SOC) is an important indicator of soil fertility. The aim of this study was to conduct a spatial assessment of erosion and its impact on SOC for specific land cover classes. Input data consisted of extensive ground truth, a digital elevation model and Landsat 7 imagery from two different seasons. Soil spectral reflectance readings were taken from soil samples in the laboratory and calibrated with results of SOC chemical analysis using regression tree modelling. The resulting model statistics for soil degradation assessments are promising (R2=0.71, RMSEV=0.32). Since the area includes rugged terrain and small agricultural plots, the decision tree models allowed mapping of land cover classes, soil erosion incidence and SOC content classes at an acceptable level of accuracy for preliminary studies. The various datasets were linked in the hot-bright spot matrix, which was developed to combine soil erosion incidence information and SOC content levels (for uniform land cover classes) in a scatter plot. The quarters of the plot show different stages of degradation, from well conserved land to hot spots of soil degradation. The approach helps to gain a better understanding of the impact of soil erosion on soil fertility and to identify hot and bright spots in a spatially explicit manner. The results show distinctly lower SOC content levels on large parts of the test areas, where annual crop cultivation was dominant in the 1990s and where cultivation has now been abandoned. On the other hand, there are strong indications that afforestations and fruit orchards established in the 1980s have been successful in conserving soil resources.

Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study

OBJECTIVE: To assess the characteristics of combination antiretroviral therapy (cART) administered concomitantly with chemotherapy and to establish prognostic determinants of patients with AIDS-related non-Hodgkin's lymphoma. METHODS: The study included 91 patients with AIDS-related non-Hodgkin's lymphoma from the Swiss HIV Cohort Study enrolled between January 1997 and October 2003, excluding lymphomas of the brain. We extracted AIDS-related non-Hodgkin's lymphoma- and HIV-specific variables at the time of lymphoma diagnosis as well as treatment changes over time from charts and from the Swiss HIV Cohort Study database. Cox regression analyses were performed to study predictors of overall and progression-free survival. RESULTS: During a median follow up of 1.6 years, 57 patients died or progressed. Thirty-five patients stopped chemotherapy prematurely (before the sixth cycle) usually due to disease progression; these patients had a shorter median survival than those who completed six or more cycles (14 versus 28 months). Interruptions of cART decreased from 35% before chemotherapy to 5% during chemotherapy. Factors associated with overall survival were CD4+ T-cell count (<100 cells/microl) (hazard ratio [HR] 2.95 [95% confidence interval (CI) 1.53-5.67], hepatitis C seropositivity (HR 2.39 [95% CI 1.01-5.67]), the international prognostic index score (HR 1.98-3.62 across categories) and Burkitt histological subtypes (HR 2.56 [95% CI 1.13-5.78]). CONCLUSIONS: Interruptions of cART were usually not induced by chemotherapy. The effect of cART interruptions on AIDS-related non-Hodgkin's lymphoma prognosis remains unclear, however, hepatitis C seropositivity emerged-as a predictor of death beyond the well-known international prognostic index score and CD4+ T-cell count.

Synergy between trovafloxacin and ceftriaxone against penicillin-resistant pneumococci in the rabbit meningitis model and in vitro

The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.

Procalcitonin and brain natriuretic peptide as parameters in the postoperative course of patients with major pulmonary resection

Postoperative infections and cardiac events are the major morbidity factors after thoracic surgery and dominating causes of death. Therefore, a sensitive blood marker is needed for an early diagnosis of complications. Twenty-two patients admitted with lung cancer were enrolled in this study. Procalcitonin, brain natriuretic peptide, C-reactive peptide and interleukin-6 levels were recorded preoperatively and postoperatively on days 1-5. Laboratory values of patients with cardiac or infectious complications were compared to patients without complications. During postoperative course procalcitonin and brain natriuretic peptide levels elevated in all patients, but both had higher peak levels in patients with infectious or cardiac complication than without these complications. Interleukin-6 levels were increased on day one and showed a slower decrease in case of complications than without complications. In general, brain natriuretic peptide and procalcitonin levels are increased in the postoperative course after major pulmonary resection, but cardiac and infectious complications are associated with higher levels and a slower decrease than without complications. Interleukin-6 levels showed a slower decrease in patients with complications in the postoperative course than without complications. So the combination of procalcitonin, brain natriuretic peptide, and interleukin-6 seems to be useful for an optimized postoperative monitoring.

Imipramine and diet counseling with psychological support in the treatment of obese binge eaters: a randomized, placebo-controlled double-blind study

This study with 31 obese binge eaters (body mass index [BMI] 39.5+/-8.6 kg/m(2) [SD]) was designed to assess whether diet counseling with psychological support and imipramine or placebo has an effect on the frequency of binge eating, body weight, and depression during an 8-week treatment phase. This was followed by an open medication-free phase of 6 months of continuous diet counseling with psychological support.

Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract

Anthropogenic nano-sized particles (NSP), ie, particles with a diameter of less than 100 nm, are generated with or without purpose as chemically and physically well-defined materials or as a consequence of combustion processes respectively. Inhalation of NSP occurs on a regular basis due to air pollution and is associated with an increase in respiratory and cardiovascular morbidity and mortality. Manufactured NSP may intentionally be inhaled as pharmaceuticals or unintentionally during production at the workplace. Hence the interactions of NSP with the respiratory tract are currently under intensive investigation. Due to special physicochemical features of NSP, its biological behaviour may differ from that of larger sized particles. Here we review two important themes of current research into the effects of NSP on the lungs: 1) The potential of NSP to cross the blood-air barrier of the lungs, thus gaining access to the circulation and extrapulmonary organs. It is currently accepted that a small fraction of inhaled NSP may translocate to the circulation. The significance of this translocation requires further research. 2) The entering mechanisms of NSP into different cell types. There is evidence that NSP are taken up by cells via well-known pathways of endocytosis but also via different mechanisms not well understood so far. Knowledge of the quantitative relationship between the different entering mechanisms and cellular responses is not yet available but is urgently needed in order to understand the effects of intentionally or unintentionally inhaled NSP on the respiratory tract.

Balancing wildlife and bioenergy values on private forestlands in the eastern Upper Peninsula of Michigan

There is interest in developing a reliable, sustainable, domestic U.S. biofuels industry. A domestic biofuels industry has the potential to provide economic, environmental, and national security benefits on a local, regional, national, and global level. The Mascoma Corporation plans to develop a cellulosic ethanol facility in Michigan’s eastern Upper Peninsula. The primary feedstock of the plant site would be trees sourced within a 150 mile supply radius. In the eastern Upper Peninsula, this radius encompasses Alger, Chippewa, Delta, Luce, Mackinac, and Schoolcraft counties. In these six counties there are 1,320,500 acres of NIPF (non-industrial private forestlands). These acres account for 40% of the total timberland in these six counties. Thus it is likely that in order for the successful implementation of a cellulosic ethanol facility the support of local NIPF owners will be necessary. This thesis presents research on how eastern Upper Peninsula forest landowners think about and manage their land. It is based on 48 in-depth interviews with these landowners. The goal was to determine how landowner values and beliefs, on a variety of issues including wildlife management, land management, biofuels development, and climate change, are expressed through both their current management decisions, and possibly their future land management decisions. Some of the values articulated by the landowners in this study included biodiversity protection, conservation of healthy game populations, and the production of high-value timber. Understanding the values and beliefs of landowners in the eastern Upper Peninsula of Michigan is critical for successfully developing a sustainable regional woody bioenergy.

Effects of forest management and time on herbaceous species dynamics in the western Upper Peninsula of Michigan

The herbaceous layer is a dynamic layer in a forest ecosystem which often contains the highest species richness in northern temperate forests. Few long-term studies exist in northern hardwood forests with consistent management practices to observe herbaceous species dynamics. The Ford Forest (Michigan Technological University) reached its 50th year of management during the winter of 2008-2009. Herbaceous species were sampled during the summers pre- and post-harvest. Distinct herbaceous communities developed in the 13-cm diameter-limit treatment and the uncut control. After the harvest, the diameter-limit treatments had herbaceous communities more similar to the 13-cm diameter-limit treatment than the uncut control; the herbaceous layer contained more exotic and early successional species. Fifty years of continuous management changed the herbaceous community especially in the diameter-limit treatments. Sites used in the development of habitat classification systems based on the presence and absence of certain herbaceous species can also be used to monitor vegetation change over time. The Guide to Forest Communities and Habitat Types of Michigan was developed to aid forest managers in understanding the potential productivity of a stand, and often aid in the development of ecologically-based forest management practices. Subsets of plots used to create the Western Upper Peninsula Guide were resampled after 10 years. During the resampling, both spring and summer vegetation were sampled and earthworm populations were estimated through liquid extraction. Spring sampling observed important spring ephemerals missed during summer sampling. More exotic species were present during the summer 2010 sampling than the summer 2000 sampling. Invasive European earthworms were also observed at all sample locations in all habitat types; earthworm densities increased with increasing habitat richness. To ensure the accuracy of the guide book, plots should be monitored to see how herbaceous communities are changing. These plots also offer unique opportunities to monitor for invasive species and the effects of a changing climate.

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study

OBJECTIVES: To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study. METHODS: Two sub-populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment-naïve patients with CD4>or=200 cells/microL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/microL without ART despite cohort follow-up. RESULTS: Median initial CD4 cell count in group A was 331 cells/microL; 31% and 10% were <200 and <50 cells/microL, respectively. Risk factors for low CD4 count were age and non-White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4>or=200 cells/microL; 18% and 2% dropped to CD4 <200 and <50 cells/microL without ART, respectively. Sub-Saharan origin was associated with lower probability of CD4 <200 cells/microL without ART during follow-up. Median CD4 count at ART initiation was 207 and 253 cells/microL in groups A and B, respectively. CONCLUSIONS: CD4<200 cells/microL and, particularly, CD4<50 cells/microL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.