Indian River Lagoon surface water improvement and management (SWIM) plan, 2002 update.

In recognition of the need to place additional emphasis on the restoration, protection, and management of the surface water resources of the state, the Florida Legislature, through the Surface Water Improvement and Management (SWIM) Act of 1987, directed the state’s water management districts to “design and implement plans and programs for the improvement and management of surface water” (Section 373.451, Florida Statutes [FS]). The SWIM legislation requires the water management districts to protect the ecological, aesthetic, recreational, and economic value of the state’s surface water bodies, keeping in mind that water quality degradation is frequently caused by point and nonpoint source pollution and that degraded water quality can cause both direct and indirect losses of aquatic habitats. This 2002 update is the second update of the Indian River Lagoon SWIM Plan. This 2002 plan update includes a status report on the state of the Lagoon, a summary of progress on projects undertaken since the last update, and recommendations for future projects and other actions over the next 5 years. (262pp.

Einfluss der S100A12-Oligomerisierung auf die Interaktion und Aktivierung der Rezeptoren RAGE und TLR-4

Das Kalzium-Bindeprotein S100A12 fungiert sowohl als Signalmolekül als auch als Biomarker bei verschiedenen (auto)inflammatorischen Erkrankungen. In Abwesenheit der Ionen Kalzium (Ca) und Zink (Zn) liegt es überwiegend als Dimer vor. Die Bindung von Ca und/oder Zn führt zu einer Konformationsänderung und damit zur Oligomerisierung. In dieser Arbeit wurden S100A12-Mutanten durch Substitution der an der Ca- oder Zn-Bindung beteiligten Aminosäuren (AS) erzeugt und auf ihre Komplexbildung sowie RAGE-/TLR-4-Bindung und -Aktivierung hin analysiert. Substitutionen der für die Zn-Bindung essentiellen AS haben weniger Einfluss auf die Komplexbildung als Mutationen der Ca-bindenden AS. Funktionelle Analysen der Mutanten zeigten, dass alle Komplexformen des S100A12 in der Lage sind, die Rezeptoren TLR-4 und RAGE zu binden. Bei Analysen zur Rezeptor-Aktivierung ist hingegen deutlich geworden, dass ausschließlich hexameres S100A12 in der Lage ist, eine Signaltransduktion über TLR 4 zu initiieren

Worldwide experience with biosimilar development

Limited access for high-quality biologics due to cost of treatment constitutes an unmet medical need in the US and other regions of the world. The term “biosimilar” is used to designate a follow-on biologic that meets extremely high standards for comparability or similarity to the originator biologic drug that is approved for use in the same indications. Use of biosimilar products has already decreased the cost of treatment in many regions of the world and now a regulatory pathway for approval of these products has been established in the US. The Food and Drug Administration (FDA) led the world with the regulatory concept of comparability and the European Medicines Agency (EMA) was the first to apply this to biosimilars. Patents on the more complex biologics, especially monoclonal antibodies, are now beginning to expire and biosimilar versions of these important medicines are in development. The new Biologics Price Competition and Innovation Act (BPCIA) allows the FDA to approve biosimilars and allows the FDA to lead on the formal designation of interchangeability of biosimilars with their reference products. The FDA's approval of biosimilars is critical to facilitating patient access to high-quality biologic medicines and will allow society to afford the truly innovative molecules currently in the global biopharmaceutical industry's pipeline

GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma

<p>Abstract</p> <p>Background</p> <p>Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene <it>GNAS1 </it>are significantly associated with better outcome in a variety of carcinomas.</p> <p>Patients</p> <p>In the present study we assessed whether the T393C SNP is also related to the clinical course in MM. 328 patients with MM were retrospectively genotyped and genotypes were correlated with clinical outcome.</p> <p>Results</p> <p>While the allele frequency in the MM group (fC 0.52) did not significantly differ from that of healthy blood donors, the T393C SNP was associated with tumor progression of MM. Carriers of the C-allele showed a significantly more severe tumor progression as estimated from the time period to develop metastasis (HR 2.2, 95% CI 1.1-3.2, p = 0.017). Proportions of 5-year metastasis-free intervals were 87.1% for TT genotypes and 66.0% for C-allele carriers. Moreover, multivariable Cox regression analysis including tumor stage and melanoma subtype proved the T393C polymorphism to be an independent factor for metastasis (p = 0.012).</p> <p>Conclusions</p> <p>In summary, the <it>GNAS1 </it>T393C SNP represents a genetic host factor for predicting tumor progression also in patients with MM; genotyping of this SNP may contribute to better define patients who could benefit from an early individualized therapy.</p

Pericardial effusion of HIV-infected patients - results of a prospective multicenter cohort study in the era of antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HlV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy.</p> <p>Methods</p> <p>The HIV-HEART (HIV-infection and HEART disease) study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20 month period in a consecutive manner from September 2004 to May 2006. The study comprehends classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation) and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography.</p> <p>Results</p> <p>802 HIV-infected patients (female: 16.6%) with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/μL. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion.</p> <p>Conclusions</p> <p>Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy.</p

A five-year observance of changes in the cardiovascular risk profile in 505 HIV-positive individuals

Purpose: Since the introduction of antiretroviral therapy (ART) and the extension of life expectancy, HIV-infected persons have shown an increasing number of cardiovascular events. The reduction of cardiovascular risk factors becomes a new challenge in HIV care. One of the main objectives of the HIV&amp;HEART study is to examine the development of cardiovascular risk factors and treatment of cardiovascular diseases. Methods: This study is an on-going, prospective, regional multicentre trial that was conducted to analyse the frequency and clinical course of cardiac disorders as well as cardiovascular risk factors in HIV-infected patients. 505 HIV-infected outpatients were recruited at baseline (BL) and re-examined during 5-year follow up (5YFU). Results: 84% of 505 eligible HIV-infected patients were male. The average age was 44.3&#x00B1;9.5 years at BL. The proportion of ART-treated patients increased from 85.7% at BL to 96.4% at 5YFU. During the 5-year observation period mean cardiovascular risk detected by Framingham score increased from 6% at BL to 10% at 5YFU. Even after adjusting for age there was a difference in the Framingham score of 2%. Between BL and 5YFU systolic blood pressure increased from 128.4&#x00B1;19.8 mmHg to 138.3&#x00B1;19.9 mmHg in spite of an intensified use of antihypertensive drugs, from 11.9% at BL to 24.0% at 5YFU. The rate of participants with adiposity, characterised by a BMI&#x3E;30, increased from 7.9% at BL to 11.2% at 5YFU. Lipid-lowering therapy was applied in 10.3% of the patients at BL and in 13.9% at 5YFU. Triglycerides (TAG)&#x2265;200 mg/dl reduced from 38.9% at BL to 36.8% at 5YFU; in contrast cholesterol values&#x2265;200 mg/dl elevated from 57.8% to 61.8%. The same trend was observed in HDL&#x2264;40 mg/dl. Here we found a change from 29.2% versus 31.3%. Doing regular sports elevated from 1.9% to 3.3%. The count of smokers increased for 2.8% and also mean pack-years changes from 24 to 26.5 pack-years. Conclusion: During a 5-year period the cardiovascular risk in Framingham score increased disproportionately high in this HIV-infected cohort even after adjusting for age. There was an increasing blood pressure although an elevated use of antihypertensive therapy. There was also a tendency of elevating BMI and an increasing trend in smoking behavior. As protective facts, we found a tendency in doing sports and a decreasing TAG value during intensifying lipid-lowering therapy. Cardiovascular risk was increasing, in spite of interventions

Study of T Cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART

<p>Abstract</p> <p>Objective</p> <p>To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART).</p> <p>Methods</p> <p>Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group). The counts of CD4⁺, CD8⁺, CD8/CD38⁺, and CD8/HLADR⁺T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline) and in the HIV negative control group. The expression of CD127 on CD3⁺T cells was measured by flow cytometry at a single time point (after 7 years) in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group.</p> <p>Results</p> <p>At baseline CD4⁺T cell counts of HIV-1-infected patients were lower than that in the control group (p < 0.01), whereas the CD8⁺, CD8/HLADR⁺and CD8/CD38⁺T cell counts were higher than those in the control group (<it>p <</it>0.01). After seven years of effective HAART, the CD4⁺T cell counts had increased and the CD8⁺T cell count had decreased, although not to the normal levels (<it>p </it>< 0.05). Both the CD8/HLADR⁺and CD8/CD38⁺T cell counts had gradually approached those of the control group (<it>p </it>> 0.05). In the ineffective HAART group, the CD8/CD38⁺T cell count had not decreased significantly, and CD8/HLADR⁺T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (<it>p </it>< 0.01). After seven years of effective HAART, IL-7 levels had gradually decreased, but were still higher than in the control group (<it>p </it>< 0.01). The CD127 expression on CD3⁺CD8⁺T cells in effective HAART patients was higher than in untreated HIV+ patients (<it>p </it>< 0.05), but was lower than that in the control group (<it>p </it>< 0.05). CD127 expression on CD3⁺CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group.</p> <p>Conclusion</p> <p><it>After seven years of </it>effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.</p

Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry

The differentiation between a pulmonary metastasis and a newly developed squamous cell carcinoma of the lung in patients with prior head and neck squamous cell carcinoma (HNSCC) is difficult due to a lack of biomarkers but is crucially important for the prognosis and therapy of the affected patient. By using high-resolution mass spectrometry in combination with stable isotope labelling by amino acids in cell culture, we identified 379 proteins that are differentially expressed in squamous cell carcinomas of the lung and the head and neck. Of those, CAV1, CAV2, LGALS1, LGALS7, CK19, and UGDH were tested by mmunohistochemistry on 194 tissue samples (98 lung and 96 HNSCCs). The combination of CAV1 and LGALS7 was able to distinguish the origin of the squamous cell carcinoma with high accuracy (area under the curve 0.876). This biomarker panel was tested on a cohort of 12 clinically classified lung tumours of unknown origin after HNSCC. Nine of those tumours were immunohistochemically classifiable