Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Highly oxygen-permeable copoly(methacrylate/siloxane)s with perfluoroalkyl ester groups

Basic materials for contact lenses were obtained by radical copolymerization of linear α,ω-bis(methacryloyloxy)-terminated oligo- and poly(dimethylsiloxane)s, methyl methacrylate and 2,2,3,3,4,4,4-heptafuorobutyl methacrylate. Oxygen permeabilities, contact angles and ball indentation hardness were determined.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Ca2+ signaling serves distinct purposes in different parts of a hair cell. The Ca2+ concentration in stereocilia regulates adaptation and, through rapid transduction-channel reclosure, underlies amplification of mechanical signals. In presynaptic active zones, Ca2+ mediates the exocytotic release of afferent neurotransmitter. At efferent synapses, Ca2+ activates the K+ channels that dominate the inhibitory postsynaptic potential. A copious supply of diffusible protein buffer isolates the three signals by restricting the spread of free Ca2+ and limiting the duration of its action. Using cDNA subtraction and a gene expression assay based on in situ hybridization, we detected abundant expression of mRNAs encoding the Ca2+ buffer parvalbumin 3 in bullfrog saccular and chicken cochlear hair cells. We cloned cDNAs encoding this protein from the corresponding inner-ear libraries and raised antisera against recombinant bullfrog parvalbumin 3. Immunohistochemical labeling indicated that parvalbumin 3 is a prominent Ca2+-binding protein in the compact, cylindrical hair cells of the bullfrog's sacculus, and occurs as well in the narrow, peanut-shaped hair cells of that organ. Using quantitative Western blot analysis, we ascertained that the concentration of parvalbumin 3 in saccular hair cells is approximately 3 mM. Parvalbumin 3 is therefore a significant mobile Ca2+ buffer, and perhaps the dominant buffer, in many types of hair cell. Moreover, parvalbumin 3 provides an early marker for developing hair cells in the frog, chicken, and zebrafish.     

Listening to Silence

SUMMARY. I have examined the function of silence - its possible role and meanings - in the psychoanalytic encounter. I have argued that silence is complementary to words in general, and to analytic free-associations in particular, and that silence in the patient is often more than just the expression of his resistance.
It could be useful to consider the silent space within a session as a sort of container of words -words that, for complex, over-determined, unconscious reasons cannot be uttered. I have insisted on the significance of analytic silences and warned against responding to them either through a retaliatory silence or through a flood of premature interpretations. These inadequate reactions often stem from the analyst's own anxiety evoked in him by the patient's silence.
Anxiety and silence are closely connected. Each silence is a compromise formation, concealing the unconscious fantasy from which it originates, while expressing a conscious one, often related to the transference situation. It is the task of the analyst to listen to his patient's silences in order to help him understand their meanings.     

Effect of Managed Care Enrollment on Primary and Repeat Cesarean Rates Among U.S. Department of Defense Health Care Beneficiaries in Military and Civilian Hospitals Worldwide, 1999–2002

Abstract: Background : In response to rising cesarean rates, it is reasonable for health care organizations to look to a managed care model as a means of controlling further rate increases. However, little conclusive evidence exists to support this solution. We undertook a study of the Department of Defense health care beneficiary population to assess the impact of enrollment in TRICARE Prime, the Department's managed care health plan, on cesarean delivery rates. Methods : Pooled hospital discharge records from 1999–2002 for live, singleton births were analyzed to calculate primary and repeat cesarean rates for TRICARE Prime and non‐Prime beneficiaries in the military and civilian hospitals that comprise the Department of Defense health care network. Stepwise logistic regression was used to calculate adjusted odds ratios for clinical indicators for each combination of health plan and hospital setting using theχ²difference(p < 0.05)to eliminate nonsignificant variables from the model. Total primary and repeat cesarean rates were compared with primary and repeat cesarean rates for women with no reported clinical complications to account for differences in case mix across subgroups. Statistical significance of the differences calculated for subgroups was assessed usingχ². Results : Primary cesarean rates were significantly lower for TRICARE Prime enrollees relative to non‐Prime beneficiaries for all race subgroups and three of five age subgroups in military hospitals and four of five age subgroups in civilian hospitals. No significant differences in repeat cesarean rates were observed between Prime and non‐Prime beneficiaries within any race or age subgroup. Breech presentation followed by dystocia, fetal distress, and other complications were significant predictors for primary cesarean. Previous cesarean delivery was the leading predictor for repeat cesarean delivery. Primary and repeat cesarean rates observed for military hospitals were consistently lower than rates observed for civilian hospitals within each health plan type and age group. Conclusions : Enrollment in the managed care health plan was significantly associated with lower risk of primary cesarean delivery relative to membership in other health plans offered to Department of Defense health care beneficiaries. Repeat cesarean rates in this population varied independently of health plan type. Primary cesarean delivery was generally associated with clinical complications, whereas previous cesarean delivery was the strongest indictor for a repeat cesarean delivery. A clear explanation of reduced cesarean rates for Prime enrollees remains elusive, but it is likely that factors beyond individual practitioner decision‐making were at work.     

Body composition in the elderly: Total body water and anthropometry

Body composition measured with isotopic dilution was compared with anthropometric measurements. The study was carried out in 47 subjects from both sexes, 65 to 92 years old. Total body water (TBW), anthropometric measurements, and dynamometry were assessed. TBW was significatively higher in men than women and decreased with age. Dynamometry and fatfree mass were well correlated (r=0.73 in males and r=0.58 in females) and significantly different between sexes. A negative correlation was found for dynamometry with age, being significant for women. Linear regression equations to predict TBW from anthropometric measurements in males and females were obtained: Males: TBW(I)=19.349+0.617 weight(kg) — 0.931 mid-arm circumference(cm)+0.122 dynamometry (kg) Females: TBW(l)=−5.531+0.343 weight(kg)-0.213 triceps skinfold (mm)+ 0.148 dynamometry(kg) + 3.424 wrist diameter (cm). This simple model is proposed for use in epidemiological and field studies where other more sophisticated methods can not be applied.