Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth

Advances in Hormone Replacement Therapy: Weight Benefits of Drospirenone, a 17alpha-Spirolactone-Derived Progestogen

Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptom relief, and may provide cardiovascular benefits in younger women initiating treatment soon after menopause. However, large surveys indicate that many symptomatic women refuse or discontinue HRT prematurely owing to fear of weight gain. A continuous combined HRT containing 17beta-estradiol (E(2)) 1 mg plus drospirenone (DRSP) 2 mg is effective in relieving menopausal symptoms and preventing postmenopausal osteoporosis. DRSP is a unique synthetic progestogen with a pharmacological profile similar to that of natural progesterone, including antialdosterone activity, a property not exhibited by other synthetic progestogens. DRSP can therefore reduce estrogen-related sodium and water retention in postmenopausal women receiving HRT via the renin-angiotensin-aldosterone system, which regulates sodium and water balance. This may translate into weight benefits. Pooled data from two placebo-controlled clinical trials (n = 333) indicated statistically significant weight loss of -1.5 kg at 6 and 12 months in postmenopausal women receiving E(2)/DRSP vs. placebo (p < 0.001). In a third randomized controlled trial (n = 1147), women receiving E(2)/DRSP maintained or lost weight, whereas weight increases were observed in women receiving E(2) monotherapy (p < 0.0125). E(2)/DRSP could help maintain or even slightly decrease body weight during treatment, potentially improving HRT acceptance and compliance

Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program

Thomas Strowitzki,1 Thomas Faustmann,2 Christoph Gerlinger,3,4 Ulrike Schumacher,5,6 Christiane Ahlers,7 Christian Seitz8 1Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Heidelberg, Germany; 2Bayer Pharma AG, Global Medical Affairs Women&rsquo;s Healthcare, Berlin, Germany; 3Bayer Pharma AG, Global Research and Development Statistics, Berlin, Germany; 4Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany; 5Jenapharm GmbH &amp; Co KG, Medical Affairs Support, Jena, Germany; 6Center for Clinical Studies, Universit&auml;tsklinikum Jena, Jena, Germany; 7Bayer Pharma AG, Global Integrated Analysis and Lifecycle Management Statistics, Wuppertal, Germany; 8Bayer Pharma AG, Global Clinical Development Therapeutic Area Primary Care and Women&rsquo;s Healthcare, Berlin, Germany Background: In four randomized, controlled, European trials, dienogest 2&nbsp;mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data&nbsp;from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis.Methods: All 332 women treated with dienogest 2&nbsp;mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics.Results: Pooled analyses of this large patient population confirmed that dienogest&nbsp;2&nbsp;mg is well tolerated, with a favorable safety profile extending over a period up to 65&nbsp;weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in &lt;10% of women. All these adverse events were generally of mild-to-moderate intensity and associated with low discontinuation rates. The bleeding pattern associated with dienogest 2&nbsp;mg was well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation. Laboratory and vital sign assessments indicated no safety concerns for dienogest. Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest&nbsp;2&nbsp;mg demonstrates therapeutic efficacy without inducing estradiol&nbsp;deficiency.Conclusion: In this pooled analysis of 332 women with endometriosis, dienogest was well tolerated with a favorable safety profile extending over a period of up to 65&nbsp;weeks. There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis. These pooled analyses from four clinical trials of dienogest&nbsp;2&nbsp;mg represent a contribution to evidence-based medicine in endometriosis, providing outcomes of potential relevance to daily practice. Keywords: progestins, endometriotic lesions, clinical trials, side effects, wome

Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy

It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients with apple allergy. The dose of 1.6 g induced oral allergy syndromes in 26.4%, 3.2 g in 15.3%, 6.3 g in 27.8%, 12.5 g in 8.3%, 25 g in 11.1%, and 50 g in 4.2% of the patients. No severe reactions occurred. None of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 g of rMal d 1 induced no reactions in three nonallergic individuals. Our approach allows straight forward, dose-defined sublingual challenge tests in a high number of birch pollen-allergic patients that inter alia can be applied to evaluate the therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy.F 4610-B28(VLID)310830

Application of a primarily deductive framework describing time consumption for hauling of logs to road-side

Forest management planning decisions are often based on the forest owner’s goals, which typically focus on economic criteria. Logging operation work productivity functions are used when costing forest operations. These functions affect the conclusions drawn during forest management analyses because different logging environments give rise to different harvesting costs. When evaluating new combinations of machines and environments, there is generally a shortage of field data on productivity that can be examined in advance. We applied a previously published deductive framework describing time consumption in forwarding to known environments, in which field studies on forwarding have been conducted and for which extensive data are available. We then adapted the deductive framework to better reproduce the results obtained in the time studies. The deductive framework accurately reproduced the observed forwarding productivities; on average, the adaptation process improved the accuracy of this reproduction. However, it may also have reduced the accuracy of individual predictions. We conclude that the deductive framework can be used as a basis for constructing work productivity functions for forest management analyses, and can serve as a foundation when constructing new productivity functions based on time study results to use when pricing forwarding