Influence of low amounts of zinc or magnesium substitution on ion release and apatite formation of Bioglass 45S5.

Magnesium and zinc ions play various key roles in the human body, being involved, among others, in skeletal development and wound healing. Zinc is also known to have antimicrobial properties. While low concentrations can stimulate cells in vitro, high concentrations of magnesium or zinc introduced into bioactive glasses significantly reduce glass degradation and ion release and inhibit apatite precipitation. On the other hand, magnesium and zinc ions improve the high temperature processing of bioactive glasses, even when present at low concentrations only. Results here show that by substituting small amounts of Mg or Zn for Ca, ion release remains high enough to allow for apatite precipitation. In addition, magnesium and zinc containing bioactive glasses are shown to be very susceptible to changes in particle size and relative surface area. For a given magnesium or zinc content in the glass, ion release and apatite formation can be enhanced dramatically by reducing the particle size, reaching comparable levels as Bioglass 45S5 of the same particle size range. Taken together, these findings suggest that when introducing these ions into bioactive glasses, ideally low Mg or Zn for Ca substitution as well as small particle sizes are used. This way, bioactive glasses combining good high temperature processing with fast ion release and apatite precipitation can be obtained, providing the potential additional benefit of releasing magnesium or zinc ions in therapeutic concentrations.

[Influence of asthma severity and asthma-specific knowledge on participation in physical education among children and young people with bronchial asthma]. / Kinder und Jugendliche mit Asthma bronchiale im Schulsport: Teilnahmehäufigkeit abhängig vom Schweregrad oder vom asthmaspezifischen Wissen durch Schulung?

BACKGROUND: Physical activity is an important part of the therapy of bronchial asthma. Even if there is exercise-induced bronchoconstriction in more or less all children with bronchial asthma, the goal is an almost complete participation in physical education lessons in school. The present study investigates their participation rate. In addition, the influence of the knowledge about asthma and the severity of the disease were studied. METHODS: A questionnaire on asthma knowledge and severity, participation rate and exercise-induced symptoms was used in 217 school children suffering from asthma (9 - 16 years). RESULTS: 80 % of the patients showed a regular participation in physical education. No correlation between participation and asthma severity was found. In contrast, a significant correlation between participation and knowledge about asthma could be demonstrated (r = 0.35, p < 0.01). The knowledge about asthma was better in school children who had completed any asthma education program in the past (19 %). However, there was generally an insufficient knowledge about asthma and exercise in the investigated group. 58 subjects were not familiar with pursed lip breathing and 112 participated in physical education lessons in spite of forgotten asthma medication. CONCLUSION: Our study demonstrates a moderate increase of participation in physical education lessons in school children with bronchial asthma during the last ten years. The participation rate correlated with asthma-specific knowledge, but not with asthma severity underlining the importance of education programs on asthma and exercise.

[Total ankle arthroplasty for rheumatoid arthritis]. / Endoprothetik des Oberen Sprunggelenks Beim Rheumatiker.

Modern second generation total ankle arthroplasty is now a serious alternative to ankle fusion in patients with rheumatoid arthritis after careful assessment of the indications. The midterm results with 10-year survival rates between 70% and 90% and the possible revision for implant exchange or arthrodesis are the reasons for the increasing importance of ankle arthroplasty. Patients with rheumatoid arthritis in particular with generally lower physical requirements can expect a pain-free function of the operated ankle for 8-10 years. In comparison to fusion ankle arthroplasty allows a significantly faster remobilization and reserves the correction capabilities of the ankle. Arthrodesis remains a valuable therapeutic alternative for severe bony destruction and instability as well as a possible fallback for failure of arthroplasty.

Mg or Zn for Ca substitution improves the sintering of bioglass 45S5.

Bioglass 45S5 is well-known for its bioactivity, but it possesses poor sintering behaviour owing to viscous flow being inhibited by the crystallisation of sodium calcium silicate phases. Mg or Zn were partially (0, 25, 50, 75%) or fully (100%) substituted for Ca on a molar base, and thermal properties (differential scanning calorimetry, dilatometry) and sintering (heating microscopy, SEM and X-ray diffraction) were investigated. Here we show that sintering can be improved significantly by partial or complete substitution of Mg or Zn for Ca, owing to a pronounced decrease in crystallisation tendency. Glass transition temperature and dilatometric softening point went through minima for mixed compositions, with random mixing of Mg/Ca or Zn/Ca ions in the glass structure and the resulting effect on configurational entropy being a likely explanation. As the onset of crystallisation did not vary much with substitution, substituted glasses possessed a wider temperature range for sintering, resulting in up to 57% and 27% sample height reduction for Mg and Zn substituted glasses, respectively, compared to only 3% height reduction for Bioglass 45S5. Taken together, these results suggest that using a combination of modifiers, particularly alkaline earths or zinc, may be a promising approach for improving the sintering of Bioglass 45S5.

Effect of poly(acrylic acid) architecture on setting and mechanical properties of glass ionomer cements.

OBJECTIVE: This work focuses on the influence of poly(acrylic acid) (PAA) architecture (linear or branched) on setting behavior and compressive strength of glass ionomer cements (GICs). METHODS: Branched and linear poly(acrylic acid)s were synthesized according to the Strathclyde methodology or by free radical polymerization. They were characterized by 1H-NMR spectroscopy and size exclusion chromatography to determine their molecular weight and size distribution. GIC setting was characterized by oscillating rheometry and time-dependent FTIR spectroscopy. In addition, compressive strength was tested on cylindrical samples (6 × 4 mm; n = 8/cement composition) after storage in deionized water at 37 °C for one day. RESULTS: We used two different routes to prepare PAA. One direct route in order to provide straightforward access to branched PAA and a two-step approach in order to get more control about the PAA molecular weight using tert-butyl acrylate (tBA) for polymerization with subsequent deprotection. Using the second approach we obtained several linear PAA of which a mixture was used in order to mimic the molecular weight and size distribution of branched PAA. This allowed the direct comparison of properties relying only on the polymer architecture. Comparing linear PAA to branched samples in general led to faster setting but at the same time decreased the compressive strength. Increasing molecular weight of branched PAA resulted in even faster GIC setting while increasing compressive strength and this correlates well with the trends reported for linear PAA in literature. Mixing of branched and linear PAA, however, turned out to be an effective way of tailoring GIC properties. SIGNIFICANCE: our results suggest that both molecular weight and dispersity need to be considered when choosing suitable PAA architecture for obtaining specific GIC properties.

Disulfide bond engineered into T4 lysozyme: stabilization of the protein toward thermal inactivation.

By recombinant DNA techniques, a disulfide bond was introduced at a specific site in T4 lysozyme, a disulfide-free enzyme. This derivative retained full enzymatic activity and was more stable toward thermal inactivation than the wild-type protein. The derivative, T4 lysozyme (Ile3----Cys), was prepared by substituting a Cys codon for an Ile codon at position 3 in the cloned lysozyme gene by means of oligonucleotide-dependent, site-directed mutagenesis. The new gene was expressed in Escherichia coli under control of the (trp-lac) hybrid tac promoter, and the protein was purified. Mild oxidation generated a disulfide bond between the new Cys3 and Cys97, one of the two unpaired cysteines of the native molecule. Oxidized T4 lysozyme (Ile3----Cys) exhibited specific activity identical to that of the wild-type enzyme when measured at 20 degrees C in a cell-clearing assay. The cross-linked protein was more stable than the wild type during incubation at elevated temperatures as determined by recovered enzymatic activity at 20 degrees C.

Catagonus, an "extinct" peccary, alive in paraguay.

A third species of peccary, discovered in the Chaco of Paraguay, is added to the living members of family Tayassuidae. It is assigned to the genus Catagonus Ameghino, heretofore considered confined to the Pleistocene. The new peccary is conspecific with Catagonus wagneri (Rusconi), a species placed in the related extinct genus Platygonus LeConte when it was described from pre-Hispanic archeological deposits of Argentina.

Carbon flow in four lake ecosystems: a structural approach.

Direct and indirect carbon fluxes in lakes Marion (British Columbia), Findley (Washington), Wingra (Wisconsin), and Mirror (New Hampshire) are compared, using budgets and input-output analysis. Overall differences in carbon flow between the lakes are shown with cycling indices of .031, .108, .572, and .661, respectively. The results suggest that lake ecosystems may be considered unique aggregatins of similar components.

Cellular and subcellular specification of Na,K-ATPase alpha and beta isoforms in the postnatal development of mouse retina.

The Na,K-ATPase is a dominant factor in retinal energy metabolism, and unique combinations of isoforms of its alpha and beta subunits are expressed in different cell types and determine its functional properties. We used isoform-specific antibodies and fluorescence confocal microscopy to determine the expression of Na,K-ATPase alpha and beta subunits in the mouse and rat retina. In the adult retina, alpha1 was found in Müller and horizontal cells, alpha2 in some Müller glia, and alpha3 in photoreceptors and all retinal neurons. beta1 was largely restricted to horizontal, amacrine, and ganglion cells; beta2 was largely restricted to photoreceptors, bipolar cells, and Müller glia; and beta3 was largely restricted to photoreceptors. Photoreceptor inner segments have the highest concentration of Na,K-ATPase in adult retinas. Isoform distribution exhibited marked changes during postnatal development. alpha3 and beta2 were in undifferentiated photoreceptor somas at birth but only later were targeted to inner segments and synaptic terminals. beta3, in contrast, was expressed late in photoreceptor differentiation and was immediately targeted to inner segments. A high level of beta1 expression in horizontal cells preceded migration, whereas increases in beta2 expression in bipolar cells occurred very late, coinciding with synaptogenesis in the inner plexiform layer. Most of the spatial specification of Na,K-ATPase isoform expression was completed before eye opening and the onset of electroretinographic responses on postnatal day 13 (P13), but quantitative increase continued until P22 in parallel with synaptogenesis.

Specificity of abnormal assembly in immunoglobulin light chain deposition disease and amyloidosis.

Although both light chain amyloidosis (AL) and deposition disease (LCDD) involve the aggregation of light chain V(L) domains into highly insoluble deposits, the factors which determine both disease onset and type (amyloid fibrils (AL) or granular deposits (LCDD)) are not clear. Previously, we showed that the AL-associated replacement Arg61 --> Asn, introduced as a point mutation into the kappa V(L) domain REI, greatly destabilizes the domain and renders it susceptible to the formation of ordered, fibril-like aggregates in vitro. The importance of Arg61 for stability may be due to the role of this residue in making a key, conserved salt bridge with Asp82 located on an adjacent loop. Here we show that an Asp82 --> Ile replacement, recently identified in a V(L) associated with LCDD, also highly destabilizes REI as a point mutation and makes it susceptible to in vitro aggregate formation. The D82I aggregate, however, is dramatically different in morphology from aggregates obtained from amyloid-associated mutants, suggesting that specific amino acid residue changes can control not only the onset of aggregation disease but also aggregate morphology and disease type.

Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity.

In expanded CAG repeat diseases such as Huntington's disease, proteins containing polyglutamine (poly(Gln)) sequences with repeat lengths of about 37 residues or more are associated with development of both disease symptoms and neuronal intranuclear inclusions (NIIs). Disease physiology in animal and cellular models does not always correlate with NII formation, however, and the mechanism by which aggregate formation might lead to cytotoxicity is unknown. To help evaluate various possible mechanisms, we determined the biophysical properties of a series of simple poly(Gln) peptides. The circular dichroism spectra of poly(Gln) peptides with repeat lengths of five, 15, 28 and 44 residues are all nearly identical and are consistent with a high degree of random coil structure, suggesting that the length-dependence of disease is not related to a conformational change in the monomeric states of expanded poly(Gln) sequences. In contrast, there is a dramatic increase in both the kinetics and the thermodynamic favorability of the spontaneous formation of ordered, amyloid-like aggregates for poly(Gln) peptides with repeat lengths of greater than 37 residues. At the same time, poly(Gln) peptides with repeat lengths in the 15-20 residue range, despite their poor abilities to support spontaneous, self-nucleated aggregation, are capable of efficiently adding to an already-formed aggregate. We also find that morphologically small, finely divided aggregates are much more efficient at recruiting poly(Gln) peptides than are large aggregates, suggesting a possible explanation for why disease pathology does not always correlate with the observable NII burden. Together, these data are consistent with a model for disease pathology in which critical cellular proteins possessing poly(Gln) sequences of modest length become inactivated when they are recruited into aggregates of an expanded poly(Gln) protein.

Physical, morphological and functional differences between ph 5.8 and 7.4 aggregates of the Alzheimer's amyloid peptide Abeta.

The Alzheimer's amyloid peptide Abeta(1-40) generates a turbid, Congo re-binding aggregation reaction product within minutes when incubated in the pH range 5 to 6. At pH 7.4, Abeta forms little or no aggregate in this time frame, requiring hours or days, rather than minutes, to complete fibril formation. The pH 5.8 aggregates are not amyloid fibrils, but rather appear in electron micrographs as a mixture of larger particles of different morphologies. These aggregates differ from classical fibrils by a number of other measures. Per mass of peptide aggregated, the pH 5.8 product binds less Congo red and thioflavin T than does aggregate grow in unstirred reactions at pH 7.4. Both the pH 5.8 and 7.4 aggregates exhibit light scattering at 90 degrees. However, while the pH 5.8 aggregate is visible in suspension by the light microscopy, and exhibits turbidity at 405 nm, the fibrils grown at pH 7.4 in an unstirred reaction are transparent. The two aggregate types do not interconvert in pH shift experiments. Most dramatically, and in contrast to fibrils grown at pH 7.4, the turbid aggregate generated at pH 5.8 is incapable of seeding fibril growth at pH 7.4. Although proteolytic processing of betaAPP to generate Abeta probably takes place in a low pH compartment of the cell, our results suggest that fibril formation is not likely to be initiated in such an environment.

Acclimation of Photosynthesis and Dark Respiration of a Submersed Angiosperm beneath Ice in a Temperate Lake.

Ceratophyllum demersum L. remained physiologically active beneath ice of a southeastern Michigan lake. The effect of seasonally low photosynthetic photon flux density (PPFD) and cold but nonfreezing temperature on whole-plant physiology was studied. Net photosynthesis was measured at six temperatures and 12 PPFDs. Net photosynthesis, soluble protein concentration, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) protein concentration, and Rubisco activity of winter plants were 32, 31, 33, and 70% lower, respectively, than those of plants collected in the summer. Optimum temperatures for net photosynthesis of winter and summer plants were 5 and 30[deg]C, respectively. Dark respiration of winter plants was up to 313% greater than that of summer plants. Reduced Rubisco activity and increased dark respiration interacted to reduce net photosynthesis. Interaction of reduced net photosynthesis and increased dark respiration increased CO2 and light compensation points and the light saturation point of winter plants. Growth of C. demersum was limited by the ambient phosphorus concentration of lake water during summer. Apical stem segments of winter-collected plants had 54 and 35% more phosphorus and nitrogen, respectively, than summer-collected plants. Physiologically active perennation beneath ice enabled C. demersum to accumulate phosphorus during the winter when it was most abundant. Partial uncoupling of phosphorus acquisition from utilization may reduce phosphorus limitation upon growth during the summer when phosphorus concentration is seasonally the lowest.

An ApoE-Abeta inhibition complex in Abeta fibril extension.

BACKGROUND: Literature reports differ dramatically in showing that apolipoprotein E either facilitates or inhibits Abeta aggregate formation in vitro. Resolution of the nature of the ApoE-Abeta interaction is critical for progress towards understanding its possible role in the modulation of Alzheimer's disease. RESULTS: Here, we show that purified ApoE-Abeta co-aggregate is a poor seed of fibril formation. We also demonstrate ApoE inhibition of Abeta fibril growth in four independent aggregation assays, arguing that the poor fibril formation observed under these conditions is real and not an analytical artifact. We also directly show ApoE binding to immobilized Abeta fibrils by surface plasmon resonance. CONCLUSIONS: The results suggest a unifying model in which ApoE binds to Abeta fibril seeds and nascent nuclei to generate stable complexes that inhibit the rapid extension of mono-component Abeta fibrils but at the same time can foster continued slow growth of mixed ApoE-Abeta aggregates. In vivo co-aggregate formation may be important in many examples of pathological protein misassembly.

Hopelessness, depression, and suicide intent.

One hundred fifty-four suicide attempters, threateners, and psychiatric controls were rated on suicide intent scales and given tests to assess hopelessness, depression and self-rated suicide risk. Ninety-four subjects were retested one month later. Both hopelessness and depression were significantly greater in suicidal subjects. In threatenets, hopelessness and depression scores differed significantly between high and low suicide intent subjects. In attempters ranked by suicide intent at time of testing, more and less suicidal subjects differed significantly in hopelessness and depression scores. Both depression and hopelessness were sensitive to changes in suicide risk during the one-month follow-up. In all analyses, hopelessness correlated more highly with suicide intent than did depression. The data were regarded as supporting the hypothesis that hopelessness is more closely related to suicide intent than is depression.

The lifetime risk of suicide in alcoholism.

Current estimates of the lifetime risk of suicide in alcoholism (11% to 15%) are shown statistically to be untenable. Examination of the mortality from suicide in all published follow-up studies of alcoholics containing the requisite data permits calculation of a much smaller lifetime suicide risk: about 2% in untreated and 2.21% in outpatient-treated probands. Studies of alcoholics identified from hospital admissions yield a lifetime risk of about 3.4% for the United States, the United Kingdom, and other English-speaking countries. It is higher in the Scandinavian and European countries with high suicide rates, but not in those with low national suicide rates. The population at risk is shown to be about half of that commonly estimated, and consists of seriously affected alcoholics. While the annual incidence of suicide in the United States is about 1.3% currently, only that quarter of the population identifiably psychiatrically ill is at significant risk. Despite the seemingly miniscule lifetime risk of 2% to 3.4%, the likelihood of suicide in conservatively diagnosed alcoholism is between 60 and 120 times that of the non-psychiatrically ill. Such alcoholism contributes about 25% of the suicides.

Suicide risk by birth cohort in the United States, 1949 to 1974.

Following the demonstration by Solomon and Hellon that in the past 30 years, successive birth cohorts in Alberta, Canada, carry successively higher suicide risks as they age, we examined data by birth cohort in the Vital Statistics of the United States by race and sex over a similar period. We found the same phenomenon, in reduced magnitude, in birth cohorts of much greater size. Not only does each successive birth cohort start with a higher suicide rate, at each successive five-year interval it has a higher rate than the preceding cohort had at that age. The regularity of this phenomenon over the past 25 years in the United States implies continually rising suicide rates in these birth cohorts. It suggests that whatever the cause of this effect, it is early and lasting. Birth cohort analysis appears to offer an important new tool for studying suicide. Its implications have only begun to be examined.

Multiple risk factors predict suicide in alcoholism.

From a study of the lives of 50 alcoholics who committed suicide, seven nonacute clinical/historical features were identified post hoc that appear to be intimately linked to suicide. They included continued drinking, major depressive episode, suicidal communication, poor social support, serious medical illness, unemployment, and living alone. This study examined whether these features are common to alcoholics generally and/or to nonalcoholics who commit suicide or if they may be specifically predictive of suicide in alcoholics. The frequencies of these factors were compared with those in an earlier sample of 32 alcoholics who committed suicide, then with data from two St Louis studies of living alcoholics and a cohort of individuals with major depressive disorder who committed suicide. The frequency of the identified items was replicated among the 32 alcoholics in a larger community sample of individuals who committed suicide. The white men from those two samples of alcoholics who committed suicide were then combined for the advantage of sample size. Six of the seven factors could be compared with a population survey sample of 106 living alcoholics and five with a clinically identified sample of 142 living alcoholics. All compared factors were significantly more frequent among those who committed suicide than among controls. Any four of the six factors identified 46 (69%) of the 67 individuals who committed suicide with few false-positive results among the controls. Regarding all seven of the identified factors, 54 (81%) of the 67 men and 64 (83%) of the entire sample of 82 individuals who committed suicide had four or more risk factors. Alcoholic women and blacks showed the same pattern as white men.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression.

Eight-seven moderately to severely depressed psychiatric outpatients were randomly assigned to 12 weeks of cognitive therapy (CT) (n = 24), pharmacotherapy (n = 24), CT plus pharmacotherapy (n = 22), or CT plus active placebo (n = 17). Seventy patients completed the treatment protocol. Seventeen dropped out before the end of the treatment period. Patients who completed treatment showed significant improvement in mean scores on two common measures of severity of depression (the Beck Depression Inventory and the Hamilton Rating Scale for Depression) between evaluation and termination. Improvement did not differ as a function of the different treatment modalities. Inclusion of dropout patients' end-point scores did not alter these results. Treatment gains in all groups were maintained at one-month follow-up assessment. A portion of this study replicated an earlier study. While the results were not identical, they indicated that either CT or antidepressant drug treatment can be effective in treating outpatients with primary, nonbipolar depression of moderate or greater severity. Combining treatments did not lead either to additive effects or negative interactions.

Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year.

Seventy patients with nonbipolar affective disorder who completed a 12-week course of either cognitive therapy (CT), pharmacotherapy, CT plus active placebo, or CT plus pharmacotherapy were assessed one month, six months, and one year after termination of active treatment. Of the 44 patients who had originally responded to treatment, 16 relapsed as defined by reentry into treatment or by self-reported depression scores in the moderately depressed range. Twenty-eight patients remained well during the one-year follow-up. Patients with relatively high levels of remaining depressive symptoms on completion of treatment relapsed more often than those who had little or no residual depression. Further, at treatment termination, patients who relapsed had significantly higher scores on a measure of dysfunctional attitudes. Patients who had received CT (with or without tricyclic antidepressants) were less likely to relapse in the one-year follow-up period than patients who received pharmacotherapy.