Human Extracellular Fluid Research Articles

L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study.

Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions

BackgroundThe choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. ObjectiveTo evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. MethodA comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. ResultThe meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of −4.49 (95% CI: −7.55, −1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: −0.85, 5.47; p = 0.15; I2 = 66%). ConclusionBRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Synergistic aggregation of the ibuprofenate anion and a a double-strand imidazolium cation into vesicles for drug delivery: a simulation study

The drug delivery process is a challenging topic that interfaces with the pharmaceutical and medical sciences. Herein the capability of a benign double-strand long-chain ionic liquid based-lipid (1,3-dimethyl-4,5-pentadecyl-imidazolium iodide ([2(Me)2(C15)im]I) in ibuprofen(Ibu) drug delivery is reported via molecular dynamics (MD) simulation for the first time. Merging the [2(Me)2(C15)im]+ cation and the ibuprofenate ([Ibu]¯) anion makes a novel ion-pair that can aggregate in a fascinating shape in aqueous media. Such aggregation benefits synergy and leads to the formation of stable cylindrical and spherical vesicles at higher and lower concentrations, respectively. These vesicles indeed involve the [Ibu]¯ as a building block of the drug carrier. The net surface charge of spherical vesicles provide the stability of their suspension; the monovalent (NaCl) solution enhances the stability of suspension due to surface charge enhancement. The coagulation of the suspended vesicles found in divalent (CaCl2) salts solution occurs through the complexation with head groups. The radial distribution function (RDF) reveals the solid-like character of the vesicle wall, evidencing the synergistic aggregation. The extended stability of spherical vesicles (involving the drug carrier ion-pair [2(Me)2(C15)im][Ibu]) in the monovalent salt solution is remarkably resembling the human body extracellular fluid and plasma.

Human concentrations of uric acid scavenges adaptive and maladaptive reactive oxygen species in isolated rat hearts subjected to ischemic stress.

Uric acid is a purine degradation product but also an important antioxidant and reactive oxygen species (ROS) scavenger. Experimental settings that mimic myocardial ischemia-reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on infarct size following ischemia-reperfusion with and without exacerbated oxidative stress due to acute pressure overload and during preconditioning. We also examined mitochondrial respiration and ROS-induced mitochondrial permeability transition pore opening. Under exacerbated ROS stress induced by high-pressure perfusion, uric acid lowered oxidative stress and reduced infarct size. In contrast, uric acid blocked cardioprotection induced by ischemic preconditioning. However, this effect was reversed by probenecid, an inhibitor of cellular uptake of uric acid. In accordance, in intact cardiomyocytes, extracellular uric acid reduced the susceptibility of mitochondria towards opening of the permeability transition pore, suggesting that uric acid may prevent ischemia-reperfusion injury due to scavenging of maladaptive ROS. Moreover, as uric acid also scavenges adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment.

Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human, and to predict drug concentration-time profiles in multiple CNS compartments on available human data of four drugs (acetaminophen, oxycodone, morphine and phenytoin).Values of the system-specific parameters in the rat CNS PBPK model were replaced by corresponding human values. The contribution of active transporters for the four selected drugs was scaled based on differences in expression of the pertinent transporters in both species. Model predictions were evaluated with available pharmacokinetic (PK) data in human brain extracellular fluid and/or cerebrospinal fluid, obtained under physiologically healthy CNS conditions (acetaminophen, oxycodone, and morphine) and under pathophysiological CNS conditions where CNS physiology could be affected (acetaminophen, morphine and phenytoin).The human CNS PBPK model could successfully predict their concentration-time profiles in multiple human CNS compartments in physiological CNS conditions within a 1.6-fold error. Furthermore, the model allowed investigation of the potential underlying mechanisms that can explain differences in CNS PK associated with pathophysiological changes. This analysis supports the relevance of the developed model to allow more effective selection of CNS drug candidates since it enables the prediction of CNS target-site concentrations in humans, which are essential for drug development and patient treatment.

Study of the effects of heat-treatment of hydroxyapatite synthesized in gelatin matrix

In the study, the isothermal thermogravimetric analysis (TGA) of hydroxyapatite synthesized in gelatin matrix (HAG) has been performed. 3 wt.% HAG samples were synthesized from the solution simulating the human extracellular fluid (SBF). X-ray diffraction and IR spectroscopy were used to determine the composition. During the experiment, increase in the calcination temperature up to 200°C–800°C was found to cause weight loss. The study of phase composition revealed that heat treatment does not affect the phase composition of the solid phase, which is composed of hydroxylapatite (HA). The prepared HAG (3 wt.% gelatin) samples are shown to have low thermal stability; the degradation of the samples occurs at 400° C.

Study of the effects of heat-treatment of hydroxyapatite synthesized in gelatin matrix

In the study, the isothermal thermogravimetric analysis (TGA) of hydroxyapatite synthesized in gelatin matrix (HAG) has been performed. 3 wt.% HAG samples were synthesized from the solution simulating the human extracellular fluid (SBF). X-ray diffraction and IR spectroscopy were used to determine the composition. During the experiment, increase in the calcination temperature up to 200°C–800°C was found to cause weight loss. The study of phase composition revealed that heat treatment does not affect the phase composition of the solid phase, which is composed of hydroxylapatite (HA). The prepared HAG (3 wt.% gelatin) samples are shown to have low thermal stability; the degradation of the samples occurs at 400°C.

R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4.

R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E2 (PGE2) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R-flurbiprofen acts through a dual mechanism: (i) it inhibits the translocation of cPLA2α to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii) R-flurbiprofen traps PGE2 inside of the cells by inhibiting multidrug resistance–associated protein 4 (MRP4, ABCC4), which acts as an outward transporter for prostaglandins. Consequently, the effects of R-flurbiprofen were mimicked by RNAi-mediated knockdown of MRP4. Our data show a novel mechanism by which R-flurbiprofen reduces extracellular PGs at physiological concentrations, particularly in cancers with high levels of MRP4, but the mechanism may also contribute to its anti-inflammatory and immune-modulating properties and suggests that it reduces PGs in a site- and context-dependent manner.

Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations.

Administration of bupropion [(±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one] and its preformed active metabolite, hydroxybupropion [(±)-1-(3-chlorophenyl)-2-[(1-hydroxy-2-methyl-2-propanyl)amino]-1-propanone], to rats with measurement of unbound concentrations by quantitative microdialysis sampling of plasma and brain extracellular fluid was used to develop a compartmental pharmacokinetics model to describe the blood-brain barrier transport of both substances. The population model revealed rapid equilibration of both entities across the blood-brain barrier, with resultant steady-state brain extracellular fluid/plasma unbound concentration ratio estimates of 1.9 and 1.7 for bupropion and hydroxybupropion, respectively, which is thus indicative of a net uptake asymmetry. An overshoot of the brain extracellular fluid/plasma unbound concentration ratio at early time points was observed with bupropion; this was modeled as a time-dependent uptake clearance of the drug across the blood-brain barrier. Translation of the model was used to predict bupropion and hydroxybupropion exposure in human brain extracellular fluid after twice-daily administration of 150 mg bupropion. Predicted concentrations indicate that preferential inhibition of the dopamine and norepinephrine transporters by the metabolite, with little to no contribution by bupropion, would be expected at this therapeutic dose. Therefore, these results extend nuclear imaging studies on dopamine transporter occupancy and suggest that inhibition of both transporters contributes significantly to bupropion's therapeutic efficacy.

Chemical Characterization of Yellow and Orange Pollen &lt;i&gt;(Helianthus annuus) &lt;/i&gt;and its Effect in the Growth of Hydroxyapatite

In this work orange pollen grains (Helianthus annuus) were immersed in a supersaturated ionic solution (similar to human extracellular fluid) during different times at 37 °C, atmospheric pressure and pH of 7.4. By Fourier transform infrared spectroscopy (FT-IR) we confirmed the presence of the functional groups carbonyl, amide I, amide II, carboxyl and phosphate in both samples. Nevertheless, yellow pollen owns a greater amount of phosphate groups than orange pollen. By scanning electron microscopy (SEM), differences in the morphology, shape and size of both samples were not observed. In orange pollen grains, amorphous agglomerates can be observed for periods smaller to 14 days and spherical structures formed by nanocrystals of laminar form were observed on their surface at 17 days. By energy dispersive spectroscopy (EDS) confirms the presence of calcium and phosphorous in the agglomerates with different Ca/P ratio and by X-ray diffraction (XRD) the hydroxyapatite (HAp) phase was verified.

Mechanism-based PK–PD model for the prolactin biological system response following an acute dopamine inhibition challenge: quantitative extrapolation to humans

The aim of this investigation was to develop a mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model for the biological system prolactin response following a dopamine inhibition challenge using remoxipride as a paradigm compound. After assessment of baseline variation in prolactin concentrations, the prolactin response of remoxipride was measured following (1) single intravenous doses of 4, 8 and 16 mg/kg and (2) following double dosing of 3.8 mg/kg with different time intervals. The mechanistic PK-PD model consisted of: (i) a PK model for remoxipride concentrations in brain extracellular fluid; (ii) a pool model incorporating prolactin synthesis, storage in lactotrophs, release into- and elimination from plasma; (iii) a positive feedback component interconnecting prolactin plasma concentrations and prolactin synthesis; and (iv) a dopamine antagonism component interconnecting remoxipride brain extracellular fluid concentrations and stimulation of prolactin release. The most important findings were that the free brain concentration drives the prolactin release into plasma and that the positive feedback on prolactin synthesis in the lactotrophs, in contrast to the negative feedback in the previous models on the PK-PD correlation of remoxipride. An external validation was performed using a dataset obtained in rats following intranasal administration of 4, 8, or 16 mg/kg remoxipride. Following simulation of human remoxipride brain extracellular fluid concentrations, pharmacodynamic extrapolation from rat to humans was performed, using allometric scaling in combination with independent information on the values of biological system specific parameters as prior knowledge. The PK-PD model successfully predicted the system prolactin response in humans, indicating that positive feedback on prolactin synthesis and allometric scaling thereof could be a new feature in describing complex homeostatic mechanisms.

Exploratory Translational Modeling Approach in Drug Development to Predict Human Brain Pharmacokinetics and Pharmacologically Relevant Clinical Doses

The central nervous system (CNS) pharmacokinetics (PK) of drugs that have pharmacological targets in the brain are not often understood during drug development, and this gap in knowledge is a limitation in providing a quantitative framework for translating nonclinical pharmacologic data to the clinical patient population. A focus of translational sciences is to improve the efficiency of clinical trial design via a more judicious selection of clinical doses on the basis of nonclinical data. We hypothesize that this can be achieved for CNS-acting drugs based on knowledge of CNS PK and brain target engagement obtained in nonclinical studies. Translating CNS PK models from rat to human can allow for the prediction of human brain PK and the human dose-brain exposure relationship, which can provide insight on the clinical dose(s) having potential brain activity and target engagement. In this study, we explored the potential utility of this translational approach using rat brain microdialysis and PK modeling techniques to predict human brain extracellular fluid PK of atomoxetine and duloxetine. The results show that this translational approach merits consideration as a means to support the clinical development of CNS-mediated drug candidates by enhancing the ability to predict pharmacologically relevant doses in humans in the absence of or in association with other biomarker approaches.

Hypertonic Saline Inhibits Arachidonic Acid Priming of the Human Neutrophil Oxidase

Although circulatory shock was initially thought to be secondary to derangements of the nervous system (“nervous collapse”) [1], the recognition of volume deficit as the underlying problem prompted the rapid expansion of fluid and resuscitation research and development. Crystalloid solutions were developed to replace volume losses and augment the circulatory system by reproducing the composition and tonicity of human intravascular extracellular fluid. Following the basic principles that sodium drives the tonicity, and water volume will follow the sodium, the logical next step in improving the volume expanding capability of a crystalloid solution was to increase the sodium concentration.

Estimating the Net Effect of Unmeasured Ions in Human Extracellular Fluid using a new Mathematical Model. Part I: Theoretical Considerations

A theoretical framework for the formulation of a derived variable to be used for the prediction of the net effect of unmeasured charged species present in human extracellular fluid was explored. This new variable was based on contemporary strong ion and classical buffer base theories and tested against the standard base excess using simulation. It proved to be more accurate in predicting the existence of unmeasured charged species in the extracellular fluid when disturbances of either strong ions, weak acids or both were present.

Reduction of Brain β-Amyloid (Aβ) by Fluvastatin, a Hydroxymethylglutaryl-CoA Reductase Inhibitor, through Increase in Degradation of Amyloid Precursor Protein C-terminal Fragments (APP-CTFs) and Aβ Clearance

Epidemiological studies suggest that statins (hydroxymethylglutaryl-CoA reductase inhibitors) could reduce the risk of Alzheimer disease. Although one possible explanation is through an effect on beta-amyloid (Abeta) metabolism, its effect remains to be elucidated. Here, we explored the molecular mechanisms of how statins influence Abeta metabolism. Fluvastatin at clinical doses significantly reduced Abeta and amyloid precursor protein C-terminal fragment (APP-CTF) levels among APP metabolites in the brain of C57BL/6 mice. Chronic intracerebroventricular infusion of lysosomal inhibitors blocked these effects, indicating that up-regulation of the lysosomal degradation of endogenous APP-CTFs is involved in reduced Abeta production. Biochemical analysis suggested that this was mediated by enhanced trafficking of APP-CTFs from endosomes to lysosomes, associated with marked changes of Rab proteins, which regulate endosomal function. In primary neurons, fluvastatin enhanced the degradation of APP-CTFs through an isoprenoid-dependent mechanism. Because our previous study suggests additive effects of fluvastatin on Abeta metabolism, we examined Abeta clearance rates by using the brain efflux index method and found its increased rates at high Abeta levels from brain. As LRP1 in brain microvessels was increased, up-regulation of LRP1-mediated Abeta clearance at the blood-brain barrier might be involved. In cultured brain microvessel endothelial cells, fluvastatin increased LRP1 and the uptake of Abeta, which was blocked by LRP1 antagonists, through an isoprenoid-dependent mechanism. Overall, the present study demonstrated that fluvastatin reduced Abeta level by an isoprenoid-dependent mechanism. These results have important implications for the development of disease-modifying therapy for Alzheimer disease as well as understanding of Abeta metabolism.

An easy to use device for lubricity examination

The stability of surgical metals implanted into patients is affected by human extracellular fluid that can enter between different components of the implant system. However data are missing on the lubricity properties of different human fluids/tissues. In our article we would like to present an easy and inexpensive device to perform and standardize implant lubricity measurements. DOI: 10.17489/biohun/2009/2/04

Proteomics of brain extracellular fluid (ECF) and cerebrospinal fluid (CSF)

Mass spectrometry has become the gold standard for the identification of proteins in proteomics. In this review, I will discuss the available literature on proteomic experiments that analyze human cerebrospinal fluid (CSF) and brain extracellular fluid (ECF), mostly obtained by cerebral microdialysis. Both materials are of high diagnostic value in clinical neurology, for example, in cerebrovascular disorders like stroke, neurodegenerative diseases like Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury and cerebral infectious and inflammatory disease, such as multiple sclerosis. Moreover, there are standard procedures for sampling. In a number of studies in recent years, biomarkers have been proposed in CSF and ECF for improved diagnosis or to control therapy, based on proteomics and mass spectrometry. I will also discuss the needs for a transition of research-based experimental screening with mass spectrometry to fast and reliable diagnostic instrumentation for clinical use.

Effects of Cross-Linking Agent on Apatite-Forming Ability and Mechanical Property of Organic-Inorganic Hybrids Based on Starch

So-called bioactive ceramics can directly bond to living bone through the apatite layer formed on their surfaces in the body. However, hard and brittle character of ceramics limits their clinical applications to low loaded portions. The apatite deposition on the bioactive ceramics is known to be triggered by a catalytic effect of silanol (Si-OH) groups formed on their surfaces and by release of calcium ions (Ca2+) that increases degree of supersaturation of the surrounding fluid with respect to the apatite. It is expected that organic modification of these components would produce bioactive materials with mechanical properties analogous to natural bone. We previously reported that bioactive organic-inorganic hybrids can be prepared from starch by modification with glycidoxypropyltrimethoxysilane (GPS) that provides with Si-OH groups and calcium chloride that releases calcium ions. In this study, we examined effect of synthetic conditions of the hybrids on their bioactivity and mechanical properties. We prepared several hybrids with different content of divinylsulfone as a cross-linking agent. Their bioactivity was examined in simulated body fluid (SBF, Kokubo solution) with inorganic ion concentrations nearly equal to those of human extracellular fluid. Materials that form the apatite on their surfaces in SBF are known to have a potential to show the bone-bonding. It was found that the added cross-linking agent did not decrease apatite-forming ability of the hybrids in SBF. Mechanical properties of the hybrids were further evaluated by a tensile test. Tensile strength and Young’s modulus increased with increasing content of divinylsulfone.

バイオミネラリゼーションに学ぶ生体材料の合成プロセス

Bioactive ceramics are now clinically used as artificial bones because they can make direct bonding to bone after implantation in bony defects. However, there are some limitations in their application due to the more brittleness and lower fractured toughness of the ceramics than those of bone. Since bone consists of hydroxyapatite and collagen, composites consisting of bone-like apatite and organic polymer is an important candidate for production of novel artificial bones. This paper reviews some of approaches to fabricate such a composite through the biomineralization-guided concept utilizing a simulated body fluid (SBF) that mimics human extracellular fluid. To deposite bone-like apatite on the organic polymer in SBF, functional groups on the polymer surface is an important parameter to induce heterogeneous nucleation of hydroxyapatite as well as increase in the degree of supersaturation with respect to hydroxyapatite through release of such ions as Ca2+. Arrangement of the functional groups on the substrates is also effective on nucleation of hydroxyapatite in addition to the kinds of the functional groups implying carboxyl groups. These molecular design brings novel biomaterials for bone substitutes with much compatibility to living bone.

Toxicity of recombinant β‐amyloid prefibrillar oligomers on the morphogenesis of the sea urchinParacentrotus lividus

A distinctive feature of Alzheimer's disease is the deposition of amyloid beta-protein (Abeta) in senile or diffuse plaques. The 42 residue beta-peptide (Abeta42) is the predominant form found in plaques. In the present work we report a high-yield expression and purification method of production of a recombinant Abeta42. The purified recombinant peptide shows characteristics similar to the synthetic human peptide. Different size aggregates, either small oligomers or larger aggregates, were obtained upon dissolving the recombinant Abeta42 peptide under different conditions at pH 7.2 or pH 3, respectively. We report a new toxicity assay on the morphogenic development of the sea urchin Paracentrotus lividus and study the toxicity of the two kinds of aggregates. Despite the difference between the ionic strength of human extracellular fluid (0.154 mol/l) and artificial sea water (0.48 mol/l), toxicity data collected in this system have an intrinsic relevance. The different ionic strength, in fact, could change the kinetics of oligomer formation, but the effect of morphogenic development reported here is related to the final oligomer sizes. Results of the toxicity assay of Abeta42 on sea urchin development also show a dose-dependent effect. After only 4 h of embryo development, one can note morphological defects in the cell membrane. Retardation of the embryo's development, along with cellular disorders visible inside the blastocoele, can be observed after 1 day of development. Cellular degeneration in two different pathological phenotypes-the occluded blastulae and the occluded prism-is present after 48 h of development. Results show that a greater effect on cell death is induced by the small oligomers stabilized under physiological conditions than at acid pH. In this case only occluded blastulae are found after 48 h of development.