Controlled release of ethanehydroxy diphosphonate from polyurethane reservoirs to inhibit calcification of bovine pericardium used in bioprosthetic heart valves

Calcification (CALC) of bioprosthetic heart valves (BHVs) fabricated from either glutaraldehyde-pretreated bovine pericardial tissue or porcine aortic valves is the most frequent cause of clinical failure of these devices. Previous studies have demonstrated that calcification is inhibited by diphosphonate compounds released into the vicinity of bioprosthetic tissue implanted subcutaneously in rats. Controlled release of the anticalcification agent ethanehydroxy diphosphonate (EHDP), as a 1:1 mixture of Na2 EHDP and CaEHDP from cylindrical polyurethane (PU) reservoirs (o.d. = 0.36 cm i.d. = 0.33 cm, length = 4 cm) fabricated by solvent casting was assessed in vitro and in vivo. The diffusivity (D), determined independently using standard diffusion cells, for ionic EHDP diffusion across the PU membrane was 1.2 x 10 cm2/s. Volume influx of buffer into the reservoirs in vitro was observed experimentally to reach a maximum at 7.8 days (288 +/- 44 [mu]l) with a biexponential decline to 147 +/- 6 [mu]l at 70 days. The cumulative EHDP released in vitro after 70 days was 4.2 +/- 0.6% (4.8 +/- 0.7 mg) compared to 15.7 +/- 3.2% (18.1 +/- 3.7 mg) in vivo (subcutaneously in 3 week-old, male, CD rats) over 21 days. The release rate of EHDP from the reservoirs was not a zero-order process. Reservoir administration of EHDP effectively inhibited pericardial BHV-CALC in 21-day subdermal explants (Ca2+ = 4.5 +/- 1.4 [mu]g Ca2+/mg tissue; control, Ca2+ = 120 +/- 13 [mu]g Ca2+/mg tissue) without diphosphonate-related untoward effects at a dose of approx. 3 mg/kg per day.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28671/1/0000488.pd

Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacements

Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic valves (BHV's). Controlled-release (paravalvar) administration of the anticalcification agent ethanehydroxydiphosphonate (EHDP), as either Na2EHDP or in combination (1:1) with the less soluble CaEHDP, from a silicone rubber matrix (20% w/w EHDP) was studied both in vitro and in vivo for the prevention of BHV CALC. Seventeen sheep (6-7 months old, male, Suffolk) underwent tricuspid valve replacement using Hancock I, 25 mm porcine aortic bioprostheses. BHV explant evaluation after 16-20 weeks revealed that two of the 7 control BHV were calcified (139 +/- 20.8 [mu]gCa2+/mg of tissue), while none of the 9 BHV retrieved from animals receiving controlled release EHDP demonstrated CALC (4.41 +/- 1.09 [mu]g Ca2+/mg of tissue). No adverse effects of EHDP on bone or calcium metabolism were noted. The cumulative percent of EHDP released per electron microprobe analysis was 40.4% +/- 9.68 (Na, CaEHDP) to 79.0% +/- 4.82 (Na2EHDP) in vivo compared to 35.7% +/- 7.72 and 78.6 +/- 11.1 in vitro, respectively. Assessment of the Young's modulus (Y) using thermomechanical analysis (TMA) revealed a 1.5-fold (Silastic Q7-4840) to 9.5-fold (Silastic 382) increase in Y following drug loading. The Y for explanted, Silastic Q7-4840 polymer matrices ranged from 2.84 x 104 to 5.57 x 105 dyne/cm2. In vitro osmotic related matrix swelling of the Na2EHDP loaded, unsealed matrices (20% w/w) after 75 days was minimized to a 35.8% increase in weight due to coincorporation of CaEHDP with Na2EHDP in a 1:1 ratio and was further reduced (22.2% increase in weight) by sealing 76% of the releasing surface, compared to Na2EHDP matrices which demonstrated a 414% and 141% increase in weight, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27902/1/0000322.pd

Immaturity of the Oculomotor Saccade and Vergence Interaction in Dyslexic Children: Evidence from a Reading and Visual Search Study

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction

Changes in Employment Uncertainty and the Fertility Intention-Realization Link: An Analysis Based on the Swiss Household Panel.

How do changes in employment uncertainty matter for fertility? Empirical studies on the impact of employment uncertainty on reproductive decision-making offer a variety of conclusions, ranging from gender and socio-economic differences in the effect of employment uncertainty on fertility intentions and behaviour, to the effect of employment on changes in fertility intentions. This article analyses the association between a change in subjective employment uncertainty and fertility intentions and behaviour by distinguishing male and female partners' employment uncertainty, and examines the variation in these associations by education. Using a sample of men and women living in a couple from the Swiss Household Panel (SHP 2002-2011), we examine through multinomial analysis how changes in employment uncertainty and selected socio-demographic factors are related to individual childbearing decisions. Our results show strong gendered effects of changes in employment uncertainty on the revision of reproductive decisions among the highly educated population

HIV Aspartyl Peptidase Inhibitors Interfere with Cellular Proliferation, Ultrastructure and Macrophage Infection of Leishmania amazonensis

Submitted by Sandra Infurna ([email protected]) on 2019-01-08T13:43:09Z No. of bitstreams: 1 Ellenf_Altoe_etal_IOC_2009.pdf: 1452755 bytes, checksum: 77127a59920cef6bca71296107f6ec63 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-08T13:51:34Z (GMT) No. of bitstreams: 1 Ellenf_Altoe_etal_IOC_2009.pdf: 1452755 bytes, checksum: 77127a59920cef6bca71296107f6ec63 (MD5)Made available in DSpace on 2019-01-08T13:51:34Z (GMT). No. of bitstreams: 1 Ellenf_Altoe_etal_IOC_2009.pdf: 1452755 bytes, checksum: 77127a59920cef6bca71296107f6ec63 (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Microbiologia Geral,. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Microbiologia Geral,. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Microbiologia Geral,. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Leishmania is the etiologic agent of leishmanisais, a protozoan disease whose pathogenic events are not well understood. Current therapy is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis

A pig model of acute Staphylococcus aureus induced pyemia

<p>Abstract</p> <p>Background</p> <p>Sepsis caused by <it>Staphylococcus aureus </it>constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with <it>S. aureus</it>, with the aim of mimicking human sepsis and pyemia.</p> <p>Methods</p> <p>The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation.</p> <p>Results</p> <p>Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study.</p> <p>Conclusion</p> <p>This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of <it>S. aureus </it>isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock.</p

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks. © The Author(s) 2010