Predicting no-show appointments in a pediatric hospital in Chile using machine learning.

The Chilean public health system serves 74% of the country's population, and 19% of medical appointments are missed on average because of no-shows. The national goal is 15%, which coincides with the average no-show rate reported in the private healthcare system. Our case study, Doctor Luis Calvo Mackenna Hospital, is a public high-complexity pediatric hospital and teaching center in Santiago, Chile. Historically, it has had high no-show rates, up to 29% in certain medical specialties. Using machine learning algorithms to predict no-shows of pediatric patients in terms of demographic, social, and historical variables. To propose and evaluate metrics to assess these models, accounting for the cost-effective impact of possible intervention strategies to reduce no-shows. We analyze the relationship between a no-show and demographic, social, and historical variables, between 2015 and 2018, through the following traditional machine learning algorithms: Random Forest, Logistic Regression, Support Vector Machines, AdaBoost and algorithms to alleviate the problem of class imbalance, such as RUS Boost, Balanced Random Forest, Balanced Bagging and Easy Ensemble. These class imbalances arise from the relatively low number of no-shows to the total number of appointments. Instead of the default thresholds used by each method, we computed alternative ones via the minimization of a weighted average of type I and II errors based on cost-effectiveness criteria. 20.4% of the 395,963 appointments considered presented no-shows, with ophthalmology showing the highest rate among specialties at 29.1%. Patients in the most deprived socioeconomic group according to their insurance type and commune of residence and those in their second infancy had the highest no-show rate. The history of non-attendance is strongly related to future no-shows. An 8-week experimental design measured a decrease in no-shows of 10.3 percentage points when using our reminder strategy compared to a control group. Among the variables analyzed, those related to patients' historical behavior, the reservation delay from the creation of the appointment, and variables that can be associated with the most disadvantaged socioeconomic group, are the most relevant to predict a no-show. Moreover, the introduction of new cost-effective metrics significantly impacts the validity of our prediction models. Using a prototype to call patients with the highest risk of no-shows resulted in a noticeable decrease in the overall no-show rate.

The incidence of psoriasis in Chile: an analysis of the National Waiting List Repository.

BACKGROUND: Psoriasis is a serious and chronic noncommunicable disease. However, the fundamental measure of disease occurrence, the incidence, has been scarcely reported globally. There are no previous studies of psoriasis incidence in Latin America. AIM: To estimate the incidence rates of psoriasis in Chile during 2016 and 2017 using an administrative database, the Waiting List Repository. METHODS: We examined referrals of psoriasis at onset, made by physicians to dermatologists, evaluated the agreement of diagnosis, and estimated the incidence of the disease considering the eligible population at risk. RESULTS: In most cases, the referrals corresponded to incident cases of psoriasis (73.3%; 95% CI: 66.6-79.2). The national incidence rates of psoriasis were 22.1 (95% CI: 21.1-23.1) and 22.7 (95% CI: 21.8-23.6) per 100 000 person-years in 2016 and 2017, respectively. The most common type of psoriasis was the late-onset type. We observed a high variation in the figures throughout the country, with a range from 0.75 (95% CI: 0.3-1.5) per 100 000 person-years in the Metropolitan region to 164.9 (95% CI: 138.6-195.1) per 100 000 person-years in the Aysen region. CONCLUSION: We describe for the first time the incidence of psoriasis in a Latin American country. Our findings could potentially guide collaborations to improve our global understanding of psoriasis in Latin America.

Perinatal nutrition interacts with genetic background to alter behavior in a parent-of-origin-dependent manner in adult Collaborative Cross mice.

Previous studies in animal models and humans have shown that exposure to nutritional deficiencies in the perinatal period increases the risk of psychiatric disease. Less well understood is how such effects are modulated by the combination of genetic background and parent-of-origin (PO). To explore this, we exposed female mice from 20 Collaborative Cross (CC) strains to protein deficient, vitamin D deficient, methyl donor enriched or standard diet during the perinatal period. These CC females were then crossed to a male from a different CC strain to produce reciprocal F1 hybrid females comprising 10 distinct genetic backgrounds. The adult F1 females were then tested in the open field, light/dark, stress-induced hyperthermia, forced swim and restraint stress assays. Our experimental design allowed us to estimate effects of genetic background, perinatal diet, PO and their interactions on behavior. Genetic background significantly affected all assessed phenotypes. Perinatal diet exposure interacted with genetic background to affect body weight, basal body temperature, anxiety-like behavior and stress response. In 8 of 9 genetic backgrounds, PO effects were observed on multiple phenotypes. Additionally, we identified a small number of diet-by-PO effects on body weight, stress response, anxiety- and depressive-like behavior. Our data show that rodent behaviors that model psychiatric disorders are affected by genetic background, PO and perinatal diet, as well as interactions among these factors.

Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects.

Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D2, are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo molecular approach to this question by performing RNA sequencing of brain tissue from mice chronically treated with the antipsychotic haloperidol or vehicle. We observed significant enrichments of haloperidol-regulated genes in schizophrenia GWAS loci and in schizophrenia-associated biological pathways. Our findings provide empirical support for overlap between genetic variation underlying the pathophysiology of schizophrenia and the molecular effects of a prototypical antipsychotic.

Electrochemical sensor for rapid determination of fibroblast growth factor receptor 4 in raw cancer cell lysates.

The first electrochemical immunosensor for the determination of fibroblast growth factor receptor 4 (FGFR4) biomarker is reported in this work. The biosensor involves a sandwich configuration with covalent immobilization of a specific capture antibody onto activated carboxylic-modified magnetic microcarriers (HOOC-MBs) and amperometric detection at disposable carbon screen-printed electrodes (SPCEs). The biosensor exhibits a great analytical performance regarding selectivity for the target protein and a low LOD of 48.2 pg mL-1. The electrochemical platform was successfully applied for the determination of FGFR4 in different cancer cell lysates without any apparent matrix effect after a simple sample dilution and using only 2.5 µg of the raw lysate. Comparison of the results with those provided by a commercial ELISA kit shows competitive advantages by using the developed immunosensor in terms of simplicity, analysis time, and portability and cost-affordability of the required instrumentation for the accurate determination of FGFR4 in cell lysates.

Disposable Amperometric Immunosensor for the Determination of Human P53 Protein in Cell Lysates Using Magnetic Micro-Carriers.

An amperometric magnetoimmunosensor for the determination of human p53 protein is described in this work using a sandwich configuration involving the covalent immobilization of a specific capture antibody onto activated carboxylic-modified magnetic beads (HOOC-MBs) and incubation of the modified MBs with a mixture of the target protein and horseradish peroxidase-labeled antibody (HRP-anti-p53). The resulting modified MBs are captured by a magnet placed under the surface of a disposable carbon screen-printed electrode (SPCE) and the amperometric responses are measured at -0.20 V (vs. an Ag pseudo-reference electrode), upon addition of hydroquinone (HQ) as a redox mediator and H2O2 as the enzyme substrate. The magnetoimmunosensing platform was successfully applied for the detection of p53 protein in different cell lysates without any matrix effect after a simple sample dilution. The results correlated accurately with those provided by a commercial ELISA kit, thus confirming the immunosensor as an attractive alternative for rapid and simple determination of this protein using portable and affordable instrumentation.

Genetic structure of phenotypic robustness in the collaborative cross mouse diallel panel.

Developmental stability and canalization describe the ability of developmental systems to minimize phenotypic variation in the face of stochastic micro-environmental effects, genetic variation and environmental influences. Canalization is the ability to minimize the effects of genetic or environmental effects, whereas developmental stability is the ability to minimize the effects of micro-environmental effects within individuals. Despite much attention, the mechanisms that underlie these two components of phenotypic robustness remain unknown. We investigated the genetic structure of phenotypic robustness in the collaborative cross (CC) mouse reference population. We analysed the magnitude of fluctuating asymmetry (FA) and among-individual variation of cranial shape in reciprocal crosses among the eight parental strains, using geometric morphometrics and a diallel analysis based on a Bayesian approach. Significant differences among genotypes were found for both measures, although they were poorly correlated at the level of individuals. An overall positive effect of inbreeding was found for both components of variation. The strain CAST/EiJ exerted a positive additive effect on FA and, to a lesser extent, among-individual variance. Sex- and other strain-specific effects were not significant. Neither FA nor among-individual variation was associated with phenotypic extremeness. Our results support the existence of genetic variation for both developmental stability and canalization. This finding is important because robustness is a key feature of developmental systems. Our finding that robustness is not related to phenotypic extremeness is consistent with theoretical work that suggests that its relationship to stabilizing selection is not straightforward.

An in vitro study on the antioxidant capacity of usnic acid on human erythrocytes and molecular models of its membrane.

Usnic acid (UA) has been associated with chronic diseases through its antioxidant action. Its main target is the cell membrane; however, its effect on that of human erythrocytes has been scarcely investigated. To gain insight into the molecular mechanisms of the interaction between UA and cell membranes human erythrocytes and molecular models of its membrane have been utilized. Dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were chosen as representative of phospholipid classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. Results by X-ray diffraction showed that UA produced structural perturbations on DMPC and DMPE bilayers. DSC studies have indicated that thermotropic behavior of DMPE was most strongly distorted by UA than DMPC, whereas the latter is mainly affected on the pretransition. Scanning electron (SEM) and defocusing microscopy (DM) showed that UA induced alterations to erythrocytes from the normal discoid shape to echinocytes. These results imply that UA molecules were located in the outer monolayer of the erythrocyte membrane. Results of its antioxidant properties showed that UA neutralized the oxidative capacity of HClO on DMPC and DMPE bilayers; SEM, DM and hemolysis assays demonstrated the protective effect of UA against the deleterious oxidant effects of HClO upon human erythrocytes.

Rapid identification and discrimination of bacterial strains by laser induced breakdown spectroscopy and neural networks.

Identification and discrimination of bacterial strains of same species exhibiting resistance to antibiotics using laser induced breakdown spectroscopy (LIBS) and neural networks (NN) algorithm is reported. The method has been applied to identify 40 bacterial strains causing hospital acquired infections (HAI), i.e. Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Salmonella pullurum and Salmonella salamae. The strains analyzed included both isolated from clinical samples and constructed in laboratory that differ in mutations as a result of their resistance to one or more antibiotics. Small changes in the atomic composition of the bacterial strains, as a result of their mutations and genetic variations, were detected by the LIBS-NN methodology and led to their identification and classification. This is of utmost importance because solely identification of bacterial species is not sufficient for disease diagnosis and identification of the actual strain is also required. The proposed method was successfully able to discriminate strains of the same bacterial species. The optimized NN models provided reliable bacterial strain identification with an index of spectral correlation higher than 95% for the samples analyzed, showing the potential and effectiveness of the method to address the safety and social-cost HAI-related issue.

Using the emerging Collaborative Cross to probe the immune system.

The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments.

Human erythrocytes and neuroblastoma cells are in vitro affected by sodium orthovanadate.

Research on biological influence of vanadium has gained major importance because it exerts potent toxic, mutagenic, and genotoxic effects on a wide variety of biological systems. However, hematological toxicity is one of the less studied effects. The lack of information on this issue prompted us to study the structural effects induced on the human erythrocyte membrane by vanadium (V). Sodium orthovanadate was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence in order that orthovanadate interacted with red cell membranes as follows: a) in scanning electron microscopy (SEM) studies it was observed that morphological changes on human erythrocytes were induced; b) fluorescence spectroscopy experiments in isolated unsealed human erythrocyte membranes (IUM) showed that an increase in the molecular dynamics and/or water content at the shallow depth of the lipids glycerol backbone at concentrations as low as 50µM was produced; c) X-ray diffraction studies showed that orthovanadate 0.25-1mM range induced increasing structural perturbation to DMPE; d) somewhat similar effects were observed by differential scanning calorimetry (DSC) with the exception of the fact that DMPC pretransition was shown to be affected; and e) fluorescence spectroscopy experiments performed in DMPC large unilamellar vesicles (LUV) showed that at very low concentrations induced changes in DPH fluorescence anisotropy at 18°C. Additional experiments were performed in mice cholinergic neuroblastoma SN56 cells; a statistically significant decrease of cell viability was observed on orthovanadate in low or moderate concentrations.

Identification and discrimination of bacterial strains by laser induced breakdown spectroscopy and neural networks.

A method based on laser induced breakdown spectroscopy (LIBS) and neural networks (NNs) has been developed and applied to the identification and discrimination of specific bacteria strains (Pseudomonas aeroginosa, Escherichia coli and Salmonella typhimurium). Instant identification of the samples is achieved using a spectral library, which was obtained by analysis using a single laser pulse of representative samples and treatment by neural networks. The samples used in this study were divided into three groups, which were prepared on three different days. The results obtained allow the identification of the bacteria tested with a certainty of over 95%, and show that only a difference between the bacteria can cause identification. Single-shot measurements were sufficient for clear identification of the bacterial strains studied. The method can be developed for automatic real time, fast, reliable and robust measurements and can be packaged in portable systems for non-specialist users.

Mn2+ exerts stronger structural effects than the Mn-citrate complex on the human erythrocyte membrane and molecular models.

While traces of manganese (Mn) take part in important and essential functions in biology, elevated exposures have been shown to cause significant toxicity. Chronic exposure to the metal leads to manganese neurotoxicity (or manganism), a brain disorder that resembles Parkinsonism. Toxic effect mechanisms of Mn is not understood, toxic concentrations of manganese are not well defined and blood manganese concentration at which neurotoxicity occurs has not been identified. There are reports indicating that the most abundant Mn-species in Mn carriers within blood is the Mn-citrate complex. Despite the well-documented information about the toxic effects of Mn, there are scarce reports concerning the effects of manganese compounds on both structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of Mn with cell membranes, MnCl(2), and the Mn-citrate complex were incubated with intact erythrocytes, isolated unsealead human erythrocyte membranes (IUM), and molecular models of the erythrocyte membrane. These consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of the erythrocyte membrane, respectively. The capacity of the Mn compounds to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction, IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). In all these systems it was found that Mn(2+) exerted considerable higher structural perturbations than the Mn-citrate complex.

Structural effects of Zn(2+) on cell membranes and molecular models.

Zinc is an essential element for nutrition as well as for the proper development and function of brain cells, and its traces are present in a wide range of foods. It is a constituent of many enzyme systems and is an integral part of insulin and of the active site of intracellular enzymes. However, excessive accumulation of zinc or its release from the binding sites may become detrimental for neurons. With the aim to better understand the molecular mechanisms of the interaction of zinc ions with cell membranes, it was incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), cholinergic murine neuroblastoma cells, and molecular models of cell membranes. These consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, particularly that of human erythrocytes, respectively. The capacity of zinc ions to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, intact human erythrocytes were observed with scanning electron microscopy (SEM), and neuroblastoma cell morphology was observed under inverted microscope. This study presents evidence that 0.1mM Zn and higher concentrations affect cell membrane and molecular models.

Human erythrocytes and molecular models of cell membranes are affected in vitro by Balbisia peduncularis (Amancay) extracts.

Balbisia peduncularis, also known as "Amancay", is a plant of the Ledocarpaceae family that can be found in the Atacama Desert in northern Chile. Infusions of the plant have long being used in traditional herbal medicine. Its chemical composition indicates the presence of flavonoids, which have antioxidant properties. Aqueous extracts from its stems were prepared to induce their interaction with human erythrocytes and their membrane models in order to elucidate whether this rare and unstudied plant produced perturbations to cell membranes. Scanning electron microscopy (SEM) of intact human red blood cells showed that the extract changed the normal erythrocytes morphology as a function of its concentration, first inducing echinocytes, and then stomatocytes and spherocytes. According to the bilayer couple hypothesis, the shape changes indicated that the flavonoids were first located in the outer monolayer of the erythrocyte membrane, and at the highest assayed concentration in both monolayers. The results obtained by fluorescence spectroscopy measurements of isolated unsealed human erythrocytes (IUM), of unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC), and by X-ray diffraction of DMPC and dimyristoylphosphatidylethanolamine (DMPE) multilayers, confirmed this conclusion. In fact, they showed that the plant aqueous extract molecules were located in both the hydrophilic polar head and in the hydrophobic acyl chain regions of the lipid bilayers. As a consequence, perturbations of the phospholipid bilayer packing arrangement were produced.

Cr(III) exerts stronger structural effects than Cr(VI) on the human erythrocyte membrane and molecular models.

Chromium exists in many oxidation states, of which only the hexavalent Cr(VI) and the trivalent Cr(III) ions are stable under environmental conditions. It is generally reported that Cr(VI) is highly toxic while Cr(III) is relatively innocuous, although others have reported just the opposite. On the other hand, despite the many studies on chromium toxicity, and particularly after the knowledge that Cr(VI) anions readily enter the erythrocytes where they are reduced to Cr(III), there are practically no reports on the structural effects induced by chromium compounds on the erythrocyte membrane. With the aim to better understand the molecular mechanisms of the interaction of Cr(III) and Cr(VI) with cell membranes, CrCl(3), and K(2)CrO(4) were incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of the erythrocyte membrane. These consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylcholine (DMPE), phospholipid classes present in the outer and inner monolayers of the erythrocyte membrane, respectively. The capacity of Cr(III) and Cr(VI) to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed with scanning electron microscopy (SEM). In all these systems, it was found that Cr(III) induced considerably higher structural perturbations than Cr(VI).

Protective effect of Ugni molinae Turcz against oxidative damage of human erythrocytes.

Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south of Chile. Infusions of its leaves have long been used in traditional native herbal medicine. The chemical composition of the leaves indicates the presence of polyphenols, which have antioxidant properties. In the present work, the antioxidant properties of U. molinae were evaluated in human erythrocytes exposed in vitro to oxidative stress induced by HClO. The experiments were carried out by scanning electron microscopy (SEM) and hemolysis measurements. The SEM observations showed that HClO induced a morphological alteration in the red blood cells from a discoid to an echinocytic form. According to the bilayer couple hypothesis, the formation of echinocytes indicates that HClO was inserted in the outer leaflet of the erythrocyte membrane. However, a concentration as low as 10 microM gallic acid equivalents (GAE) U. molinae aqueous extract neutralized the shape change effect of HClO applied in a concentration as high as 0.25 mM. The significant protection of U. molinae aqueous extract was also shown in the hemolysis experiments. In fact, very low concentrations of the extract considerably reduced the deleterious capacity of HClO to induce hemolysis in red blood cells. It is concluded that the location of the extract components into the membrane bilayer and the resulting restriction on its fluidity might hinder the diffusion of HClO and its consequent damaging effects. This conclusion can also imply that this restriction could apply to the diffusion of free radicals into cell membranes and the subsequent decrease of the kinetics of free radical reactions.

Human erythrocytes are affected in vitro by extracts of Ugni molinae leaves.

Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south of Chile. Infusions of their leaves have long been used in traditional native herbal medicine. The chemical composition of the leaves indicates the presence of polyphenols, which have antioxidant properties. In order to evaluate the mechanisms of their antioxidant properties and the toxicity of the aqueous extracts of leaves, the extracts were induced to interact with human red cells, their isolated unsealed membranes (IUM) and large unilamellar vesicles (LUV) of dimyristoylphosphatidyltidylcholine (DMPC), representative of phospholipid classes located in the outer monolayer of the erythrocyte membrane. Scanning electron microscopy (SEM) observations indicated that the extracts achieved a significant alteration in the shape of the erythrocytes as they changed their discoid shape to echinocytes. According to the bilayer couple hypothesis, the shape change indicates that the polyphenols were located in the outer moiety of the red cell membrane. This conclusion was confirmed by the fluorescence experiments performed in IUM and DMPC LUV. In fact, the extracts produced slight initial increases followed by sharp decreases at higher concentrations in the anisotropy and general polarization parameters. These results imply that the extracts induced structural perturbations in the acyl chain and polar group packing arrangements of the erythrocyte IUM and DMPC LUV lipid bilayers: first ordering and afterwards disordering them as the extract concentration increased.

Human erythrocytes are affected by the organochloride insecticide chlordane.

Chlordane is a widely used organochlorine insecticide. In order to evaluate its perturbing effect upon the morphology of human erythrocytes it was caused to interact with human red cells and molecular models of cell membranes. These consisted in bilayers of dimyristoylphosphatidylethanolamine (DMPE) and of dimyristoylphosphatidylcholine (DMPC), representative of phospholipid classes located in the inner and outer monolayers of the erythrocyte membrane, respectively. Scanning electron microscopy (SEM) observations indicated that this pesticide induced a significant alteration in the shape of the erythrocytes as they changed their discoid shape to spherocytes. According to the bilayer couple hypothesis, the shape changes induced in erythrocytes by foreign molecules are due to differential expansion of their two monolayers. The fact that chlordane produced spherocytes would indicate that the pesticide was equally located in the outer and the inner moieties of the red cell membrane. This conclusion was supported by the results obtained from X-ray diffraction studies. These showed that the hydrophobic and polar head regions of DMPC bilayers were perturbed when the insecticide was in a 1:10 molar ratio with respect to the lipid. These results were confirmed by the fluorescence experiments performed in DMPC large unilamellar vesicles (LUV). Chlordane produced a sharp decrease in the anisotropy and general polarization parameters in the 0-0.1 mM range, implying an increase in the fluidity at the acyl chain and polar region of DMPC. On the other hand, the bilayer structure of DMPE was perturbed in a fashion similar to that observed by X-ray diffraction in DMPC, a fact that explains the morphological change induced by chlordane to the human erythrocytes.

Structural effects of titanium citrate on the human erythrocyte membrane.

The structural effects of titanium citrate on the human erythrocyte membrane were studied through its interaction with intact erythrocytes and isolated unsealed human erythrocyte membranes (IUM). The studies were carried out by scanning electron microscopy and fluorescence spectroscopy, respectively. Titanium citrate induced shape changes in erythrocytes, which were damaged and ruptured leaving empty and retracted membranes. Fluorescence spectroscopy measurements in IUM indicated a disordering effect at both the polar head group and the acyl chain packing arrangements of the membrane phospholipid bilayer. Titanium citrate also interacted with molecular models of the erythrocyte membrane consisting in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representing classes of phospholipids located in the outer and inner monolayers of the erythrocyte membrane, respectively. X-ray diffraction indicated that titanium citrate induced structural perturbation of the polar head group and of the hydrophobic acyl regions of DMPC, while the effects on DMPE bilayers were negligible. This conclusion is supported by fluorescence spectroscopy measurements on DMPC large unilamellar vesicles. All these findings indicate that the structural perturbations induced by titanium to human erythrocytes can be extended to other cells, thereby affecting their functions.