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Understanding peri-implant endosseous healing.

If dental implantology is an increasingly successful treatment modality, why should we still need to understand the mechanisms of peri-implant bone healing? Are there differences in cortical and trabecular healing? What does "poor quality" bone mean? What stages of healing are most important? How do calcium phosphate-coated implants accelerate healing? What is the mechanism of bone bonding? While there are still many aspects of peri-implant healing that need to be elucidated, it is now possible to deconvolute this biological reaction cascade, both phenomenologically and experimentally, into three distinct phases that mirror the evolution of bone into an exquisite tissue capable of regeneration. The first and most important healing phase, osteoconduction, relies on the recruitment and migration of osteogenic cells to the implant surface, through the residue of the peri-implant blood clot. Among the most important aspects of osteoconduction are the knock-on effects generated at the implant surface, by the initiation of platelet activation, which result in directed osteogenic cell migration. The second healing phase, de novo bone formation, results in a mineralized interfacial matrix equivalent to that seen in the cement line in natural bone tissue. These two healing phases, osteoconduction and de novo bone formation, result in contact osteogenesis and, given an appropriate implant surface, bone bonding. The third healing phase, bone remodeling, relies on slower processes and is not considered here. This discussion paper argues that it is the very success of dental implants that is driving their increased use in ever more challenging clinical situations and that many of the most important steps in the peri-implant healing cascade are profoundly influenced by implant surface microtopography. By understanding what is important in peri-implant bone healing, we are now able to answer all the questions listed above.

Bone Density↗

[Grain protein content in wheat: genetics of the character and some predictions for its improvement in common wheat].

The results of studies on genetic control of the grain protein content character in common wheat and the attempts of its improvement using traditional breeding approaches and methods of experimental mutagenesis and introgressive hybridization are presented. The evolution of the views on the genetic structure of the character is considered. Possible explanations are given to the fact that the attempts to significantly improve the character in question in common wheat cultivars have failed in spite of long-term genetic and selection studies. Possible lines of further investigation of genetic control of grain protein content and its increase in common wheat are discussed.

Crops, Agricultural↗

Platelet-activating factor antagonists treatment protects against postischemic acute renal failure in rats.

Platelet-activating factor (PAF-acether) has been shown to be produced by the kidney and to sharply reduce glomerular filtration rate (GFR) and renal plasma flow (RPF). Thus, PAF-acether could be a possible mediator of the reduction of GFR and RPF in ischemic-induced acute renal failure (ARF). We have assayed the effect of inhibiting the interaction of PAF-acether with its receptor using two specific PAF-acether antagonists, BN-52021 and alprazolam, on the evolution of the GFR and RPF, in the experimental model of ARF induced in rats by clamping the left artery for 60 min. In addition, we have measured arteriovenous differences in PAF-acether concentration, as well as PAF-acether content in glomeruli from rats with ARF pretreated or not with BN-52021. In metabolic cage studies, plasma creatinine increased more in the untreated than in the BN-52021-treated group, whereas creatinine clearance was higher in treated than in untreated rats. In acute clearance experiments, after renal artery clamping, untreated rats showed a marked oliguria and reduction of the inulin clearance (greater than 99%), which showed no recovery 90 min after clamp release, whereas GFR reached values above 0.1 ml/min in the rats treated with BN-52021 or alprazolam, with clearly significant statistical differences. Results of p-aminohippurate clearance were similar to those of GFR. Glomeruli from rats with ARF had greater amounts of PAF-acether than glomeruli from normal rats, whereas glomeruli from BN-52021-treated rats with ARF produced intermediate amounts. These results provide evidence for a role for PAF-acether in the genesis of this model of experimental ARF.

Acute Kidney Injury↗

The role of retinal pigment epithelium in the involution of subretinal neovascularization.

The extravascular milieu around laser-induced experimental subretinal neovascularization (SRN) was studied during the evolution of the neovascular membrane from its early leaky stage to its late involuted stage. When the first signs of visible leakage appeared on angiography, newly formed vessels were spread in the subretinal space around the break in Bruch's membrane, fluid was accumulating in the subretinal space, and retinal pigment epithelial (RPE) cells were proliferating in a papillary pattern around the newly formed vessels; the RPE proliferation began with the undamaged cells at the edges of the laser injury. With further maturation, the RPE continued to envelope the subretinal vessels. This RPE proliferation was associated with the disappearance of fluid between the enveloped vessels and the sensory retina, and the gradual cessation of fluorescein leakage during angiography. At the end of the involution process, when the neovascular membrane no longer demonstrated any leakage, the subretinal vessels were found to be tightly enveloped by RPE cells, and no fluid separated them from the sensory retina. The authors' results suggest that involution of the neovascular membrane with maturation, as demonstrated by the cessation of visible fluorescein leakage, is the result of RPE proliferation that tightly envelopes the newly formed vessels and probably resorbs the previously accumulated subretinal fluid, as well as preventing its further accumulation in the subretinal space.

Animals↗

Phosphomycin levels in serum and interstitial tissue fluid in a multiple dosage regimen in rabbits.

The evolution of phosphomycin (Fosfocina), levels in serum and experimentally induced interstitial tissue fluid and the access of the drug to different organs were studied in rabbits after the administration of a single dose of 60 mg/kg and during a multiple dosage regimen of 60 mg/kg/6 h over three days. Following the administration of a single dose a Cmax value of phosphomycin in interstitial tissue fluid of 80.4 micrograms/ml was reached at 1.2 h. The elimination half-life of the drug from the systemic circulation after a single dose had a value of 1.6 h, and was not significantly different from the value found for the same parameter in the multiple dosage regimen. The disappearance half-life of phosphomycin from interstitial tissue fluid, with a value of 1.9 h for the single dose schedule, was not significantly different from the value of the disappearance half-life of the drug from interstitial tissue fluid in the multiple dosage regimen. Finally, the results of the present study confirm the linearity of phosphomycin kinetics, at least in the conditions studied, and show that the drug is not accumulated in the organs considered.

Animals↗

[Regulation of erythropoiesis in the rat fetus: role of spleen and bone marrow in case of deficiency of hepatic erythropoietic activity].

At the end of intra-uterine life in the rat, hepatic erythron evolution is governed by corticosteroids and it is experimentally possible to prematurely deprive the foetus of a large part of its hepatic erythropoietic tissue by inflicting repeated stress in the pregnant animal. This experimentally induced deficiency of the hepatic erythron leads to an anticipated erythroid activity in the bone marrow. Splenectomy in such fetuses has shown that the spleen does not play a major role in producing circulating anucleated erythroid cells before term.

Animals↗

Analysis of connectivity in the cat cerebral cortex.

The mammalian cerebral cortex is innervated by a large number of corticocortical connections. The number of connections makes it difficult to understand the organization of the cortical network. Nonetheless, conclusions about the organization of cortical systems drawn from examining connectional data have often been made in a speculative and informal manner, unsupported by any analytic treatment. Recently, progress has been made toward more systematic ways of extracting organizing principles from data on the network of connections between cortical areas of the monkey. In this article, we extend these approaches to the cortical systems of the cat. We collated information from the neuroanatomical literature about the corticocortical connections of the cat. This collation incorporated 1139 reported corticocortical connections between 65 cortical areas. We have previously used an optimization technique (Scannell and Young, 1993) to analyze this database in order to represent the connectional organization of cortical systems in the cat. Here, we report the connectional database and analyze it in a number of further ways. First, we employed rules from Felleman and Van Essen (1991) to investigate hierarchical relations among the areas. Second, we compared quantitatively the results of the optimization method with the results of the hierarchical method. Third, we examined quantitatively whether simple connection rules, which may reflect the development and evolution of the cortex, can account for the experimentally identified corticocortical connections in the database. The results showed, first, that hierarchical rules, when applied to the cat visual system, define a largely consistent hierarchy. Second, in both auditory and visual systems, the ordering of areas by hierarchical analysis and by optimization analysis was statistically significantly related. Hence, independent analyzes concur broadly in their ordering of areas in the cortical hierarchies. Third, the majority of corticocortical connections, and much of the pattern of connectivity, were accounted for by a simple "nearest-neighbor-or-next-door-but-one" connection rule, which may suggest one of the mechanisms by which the development of cortical connectivity is controlled.

Animals↗

[Study of humoral immunity in human biharziasis. Value of E.L.I.E.D.A. (enzyme-linked immunoelectrodiffusion assay)].

With a view to sensitize the immuno-electro-diffusion test (I.E.D.) and determine the immunoglobulins involved in the antigen-antibody reaction, the authors have improved the I.E.D. test by coupling it with an enzymatic technique. The precipitated immune-complexes are treated with antibodies conjugated with an enzyme specific for each class of immuno-globulins. This association realizes the E.L.I.E.D.A. (enzyme-linked immuno-electro-diffusion-assay). The sensitivity and specificity of the method are excellent, and should allow to follow the qualitative evolution of the bilharzian antibody in natural and experimental affections.

Antibodies↗

Enhanced lipid peroxidation in hepatic cirrhosis.

BACKGROUND: Lipid peroxidation is thought to play a role in the evolution of liver damage, based on evidence in experimental models. However, evidence that lipid peroxidation occurs in patients with liver disease remains to be provided. We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of arachidonic acid, in patients with liver cirrhosis. METHODS: In 42 patients with hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia, carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d. vitamin E administration. RESULTS: Cirrhotic patients had significant higher 8-epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0-812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8-epi Prostaglandin F2 alpha above the range in controls were more likely to have moderate or severe than mild liver failure (p < 0.004). They also had lower factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range): 342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04]. CONCLUSION: This study demonstrated that lipid peroxidation is increased in vivo in patients with cirrhosis and suggests that oxidant stress might contribute to the deterioration of liver disease.

Adult↗

Aging effect on the phase evolution of water-based sol-gel hydroxyapatite.

In a number of recent reports on the synthesis of sol-gel hydroxyapatite, aging of the precursor solution has been found to be critical in developing an apatitic phase. Critical aging time is required to complete reaction between Ca and P molecular precursors to form a desired intermediate complex that permits a further transformation to apatite phase under appropriate thermal treatment. In this investigation, we employed a water-based sol-gel process recently developed to fabricate hydroxyapatite at relatively low temperatures. The aging effect on apatite formation was systematically studied in terms of aging time and temperature. Experimental results show that the aging time is considerably reduced as aging temperature rises. Long-term thermal aging was unfavorable for apatite formation. The optimal aging parameters for apatite formation were experimentally determined, which was further consolidated into a phase evolution map. Aging kinetic was investigated by monitoring the variation of solution pH, following the determination of an apparent activation energy, which has a value as high as 10.35 kcal/mol, for the chemical reaction occurring upon aging. Optimal solution chemistry was elucidated based on the corresponding phase evolution map.

Biocompatible Materials↗

The S2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies.

Equine infectious anemia virus (EIAV) is genetically one of the simplest lentiviruses in that the viral genome encodes only three accessory genes, tat, rev, and S2. Although serological analyses demonstrate the expression of the S2 protein in persistently infected horses, the role of this viral gene remains undefined. We recently reported that the S2 gene is not essential for EIAV replication in primary equine macrophages, as EIAV mutants lacking the S2 gene replicate to levels similar to those of the parental virus (F. Li, B. A. Puffer, and R. C. Montelaro, J. Virol. 72:8344-8348, 1998). We now describe in vivo studies that examine the evolution and role of the S2 gene in ponies experimentally infected with EIAV. The results of these studies reveal for the first time that the S2 gene is highly conserved during persistent infection and that deletion of the S2 gene reduces viral virulence and virus replication levels compared to those of the parental virus containing a functional S2 gene. These data indicate that the EIAV S2 gene is in fact an important determinant of viral replication and pathogenic properties in vivo, despite the evident lack of S2 influence on viral replication levels in vitro. Thus, these observations suggest in vivo functions of EIAV S2 that are not adequately reflected in simple infections of cultured cells, including natural target macrophages.

Amino Acid Sequence↗

Mechanisms of pattern formation in development and evolution.

We present a classification of developmental mechanisms that have been shown experimentally to generate pattern and form in metazoan organisms. We propose that all such mechanisms can be organized into three basic categories and that two of these may act as composite mechanisms in two different ways. The simple categories are cell autonomous mechanisms in which cells enter into specific arrangements ('patterns') without interacting, inductive mechanisms in which cell communication leads to changes in pattern by reciprocal or hierarchical alteration of cell phenotypes ('states') and morphogenetic mechanisms in which pattern changes by means of cell interactions that do not change cell states. The latter two types of mechanism can be combined either morphostatically, in which case inductive mechanisms act first, followed by the morphogenetic mechanism, or morphodynamically, in which case both types of mechanisms interact continuously to modify each other's dynamics. We propose that this previously unexplored distinction in the operation of composite developmental mechanisms provides insight into the dynamics of many developmental processes. In particular, morphostatic and morphodynamic mechanisms respond to small changes in their genetic and microenvironmental components in dramatically different ways. We suggest that these differences in 'variational properties' lead to morphostatic and morphodynamic mechanisms being represented to different extents in early and late stages of development and to their contributing in distinct ways to morphological transitions in evolution.

Animals↗

Application of mass and energy balance regularities in fermentation. Reprinted from Biotechnology and Bioengineering, Vol. XX, No. 10, Pages 1595-1621 (1978).

Material and energy balances for fermentation processes are developed based on the facts that the heat of reaction per electron transferred to oxygen for a wide variety of organic molecules, the number of available electrons per carbon atom in biomass, and the weight fraction carbon in biomass are relatively constant. Mass-energy balance equations are developed which relate the biomass energetic yield coefficient to sets of variables which may be determined experimentally. Organic substrate consumption, biomass production, oxygen consumption, carbon dioxide production, heat evolution, and nitrogen consumption are considered as measured variables. Application of the balances using direct and indirect methods of yield coefficient estimation is illustrated using experimental results from the literature. Product formation is included in the balance equations and the effect of product formation on biomass yield estimates is examined. Application of mass-energy balances in the optimal operation of continuous single-cell protein production facilities is examined, and the variation of optimal operating conditions with changes in yield are illustrated for methanol as organic substrate.

Electrons↗

Wright's shifting balance theory: an experimental study.

Experimental confirmation of Wright's shifting balance theory of evolution, one of the most comprehensive theories of adaptive evolution, is presented. The theory is regarded by many as a cornerstone of modern evolutionary thought, but there has been little direct empirical evidence supporting it. Some of its underlying assumptions are viewed as contradictory, and the existence and efficacy of the theory's fundamental adaptive process, interdemic selection, is the focus of controversy. Interdemic selection was imposed on large arrays of laboratory populations of the flour beetle Tribolium castaneum in the manner described by Wright: the differential dispersion of individuals from demes of high fitness into demes of low fitness. A significant increase in average fitness was observed in the experimental arrays when compared to control populations with equivalent but random migration rates. The response was not proportional to the selection differential: The largest response occurred with interdemic selection every two generations rather than every generation or every three generations. The results indicate that the interdemic phase of Wright's shifting balance theory can increase average fitness and suggest that gene interactions are involved in the observed response.

Adaptation, Physiological↗

Evo-devo and constraints on selection.

Developmental bias, or genetic channeling, can influence the tempo and direction of evolution and, thus, become reflected in patterns of biodiversity. Twenty years ago, this notion rested on armchair descriptions of potential constraints on evolution. Now, a broad evo-devo approach involving both evolutionary and developmental genetics provides experimental analysis of such bias, revealing how shared genetic or developmental pathways among morphological traits contribute to the evolution of complexity and diversity, and that developmental bias itself evolves, generating variation in evolvability. As I discuss here, it is now possible to determine the relative importance of natural selection and of genetical and developmental architecture as determinants of organic diversity, particularly for examples of adaptive radiations and parallel evolution.

Animals↗