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We have previously shown that the CBb subunit of crotoxin, a β-neurotoxin with phospholipase A 2 (PLA 2 ) activity, targets the human ΔF508CFTR chloride channel implicated in cystic fibrosis (CF). By direct binding to the nucleotide binding domain 1 (NBD1) of ΔF508CFTR, this neurotoxic PLA 2 acts as a potentiator increasing chloride channel current and corrects the trafficking defect of misfolded ΔF508CFTR inside the cell. Here, for a therapeutics development of new anti-cystic fibrosis agents, we use a structure-based in silico approach to design peptides mimicking the CBb-ΔF508NBD1 interface. Combining biophysical and electrophysiological methods, we identify several peptides that interact with the ΔF508NBD1 domain and reveal their effects as potentiators on phosphorylated ΔF508CFTR. Moreover, protein-peptide interactions and electrophysiological studies allowed us to identify key residues of ΔF508NBD1 governing the interactions with the novel potentiators. The designed peptides bind to the same region as CBb phospholipase A 2 on ΔF508NBD1 and potentiate chloride channel activity. Certain peptides also show an additive effect towards the clinically approved VX-770 potentiator. The identified CF therapeutics peptides represent a novel class of CFTR potentiators and illustrate a strategy leading to reproducing the effect of specific protein-protein interactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

CRISPR-Cas is a prokaryotic adaptive immune system that functions by incorporating fragments of foreign DNA into CRISPR arrays. The arrays containing spacers derived from foreign DNA are transcribed, and the transcripts are processed to generate spacer-containing mature CRISPR-RNAs that are employed as guides to specifically recognize and cleave the DNA or RNA of the cognate parasitic genetic elements. The CRISPR-Cas systems show remarkable complexity and diversity of molecular organization and appear to be involved in various cellular functions that are distinct from, even if connected to, adaptive immunity. In this review, we discuss some of such functional links of CRISPR-Cas systems including their effect on horizontal gene transfer that can be either inhibitory or stimulatory, connections between CRISPR-Cas and DNA repair systems as well as programmed cell death and signal transduction mechanisms, and potential role of CRISPR-Cas in transposon integration and plasmid maintenance. The interplay between the primary function of CRISPR-Cas as an adaptive immunity mechanism and these other roles defines the richness of the biological effects of these systems and affects their spread among bacteria and archaea., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Metabolic response to severe trauma requires early nutritional resuscitation. Carnitine is essential for lipolysis, the energy source during this hypercatabolic phase. However l-carnitine is not present in nutritional replacement solutions. Furthermore, free carnitine depletion, defined as carnitine plasma level under 36μmol/L, was not adequately reported in adult patients with severe trauma. The aim of this study was to assess plasma free carnitine levels and factors of variation in severe trauma., Method: Our observational study concerned 38 trauma patients including 18 with traumatic brain injury (TBI). On the third day after trauma, plasma free carnitine concentration was determined (by enzymatic method) while patients received artificial nutrition., Results: Low plasmatic free carnitine concentration was evidenced in 95% of the patients with a median value of 18μmol/L (11-47). Univariate analysis showed that mean arterial pressure, serum urea, CKD-EPI and patients with TBI were significantly associated with plasma free carnitine concentration less than 18μmol/L. Lower plasma free carnitine concentration was observed in the group of patients with TBI with 17.72μmol/L (11-36) versus 21.5μmol/L (11-47) for others patients (p=0.031). Logistic regression analysis showed that severe trauma with TBI and CKD-EPI above 94mL/min/1.73m2 appeared to be independent predictor of lower free carnitine plasmatic concentration (Goodness of fit=0.87 and AUC=0.89)., Conclusion: Our observations support hypotheses that plasma free carnitine concentration is lowered in severe injured patients especially for TBI patients and patients with estimated GFR above 94mL/min/1.73m 2 ., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Deletion of Phe508 in the nucleotide binding domain (∆F508-NBD1) of the cystic fibrosis transmembrane regulator (CFTR; a cyclic AMP-regulated chloride channel) is the most frequent mutation associated with cystic fibrosis. This mutation affects the maturation and gating of CFTR protein. The search for new high-affinity ligands of CFTR acting as dual modulators (correctors/activators) presents a major challenge in the pharmacology of cystic fibrosis. Snake venoms are a rich source of natural multifunctional proteins, potential binders of ion channels. In this study, we identified the CB subunit of crotoxin from Crotalus durissus terrificus as a new ligand and allosteric modulator of CFTR. We showed that CB interacts with NBD1 of both wild type and ∆F508CFTR and increases their chloride channel currents. The potentiating effect of CB on CFTR activity was demonstrated using electrophysiological techniques in Xenopus laevis oocytes, in CFTR-HeLa cells, and ex vivo in mouse colon tissue. The correcting effect of CB was shown by functional rescue of CFTR activity after 24-h ΔF508CFTR treatments with CB. Moreover, the presence of fully glycosylated CFTR was observed. Molecular docking allowed us to propose a model of the complex involving of the ABCβ and F1-like ATP-binding subdomains of ΔF508-NBD1. Hydrogen-deuterium exchange analysis confirmed stabilization in these regions, also showing allosteric stabilization in two other distal regions. Surface plasmon resonance competition studies showed that CB disrupts the ∆F508CFTR-cytokeratin 8 complex, allowing for the escape of ∆F508CFTR from degradation. Therefore CB, as a dual modulator of ΔF508CFTR, constitutes a template for the development of new anti-CF agents., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The crystal structure of crotoxin, a potent presynaptic neurotoxin from Crotalus durissusterrificus, was solved at 1.35 Å resolution. It shows the architecture of the three disulfide-linked polypeptide chains (α, β, and γ) of the acidic subunit CA noncovalently complexed with the basic phospholipase A(2) (PLA(2)) subunit CB. The unique structural scaffold of the association of the CA and CB subunits indicates that posttranslational cleavage of the pro-CA precursor is a prerequisite for the assembly of the CA-CB complex. These studies provide novel structural insights to explain the role of the CA subunit in the mechanism of action of crotoxin. The crystal structure of the highly toxic and stable CA(2)CBb complex crystallized here allows us to identify key amino acid residues responsible for significant differences in the pharmacological activities of the two classes of crotoxin complexes. In particular, we show that critical residues Trp31 and Trp70 of the CBb subunit establish intermolecular polar contacts with Asp99 and Asp89, respectively, of the β-chain of CA(2) and contribute to the stability and toxicity of the CA(2)CBb complex. These interactions also lead to decreased PLA(2) activity by partially blocking substrate access to the catalytic dyad and by masking several interfacial binding surface residues important for PLA(2) interaction with phospholipids. Identification of the binding interface between the CA subunits and the CB subunits of crotoxin is important for the structure-based design of antineurotoxic inhibitors. Since crotoxin displays numerous physiological functions, including antitumoral properties, knowledge of its three-dimensional structure will be useful for the understanding of these diverse effects., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Apical membrane antigen 1 (AMA1) has an important, but as yet uncharacterised, role in host cell invasion by the malaria parasite, Plasmodium. The protein, which is quite conserved between Plasmodium species, comprises an ectoplasmic region, a single transmembrane segment and a small cytoplasmic domain. The ectoplasmic region, which can induce protective immunity in animal models of human malaria, is a leading vaccine candidate that has entered clinical trials. The monoclonal antibody F8.12.19, raised against the recombinant ectoplasmic region of AMA1 from Plasmodium vivax, cross-reacts with homologues from Plasmodium knowlesi, Plasmodium cynomolgi, Plasmodium berghei and Plasmodium falciparum, as shown by immunofluorescence assays on mature schizonts. The binding of F8.12.19 to recombinant AMA1 from both P. vivax and P. falciparum was measured by surface plasmon resonance, revealing an apparent affinity constant that is about 100-fold weaker for the cross-reacting antigen when compared to the cognate antigen. Crystal structure analysis of Fab F8.12.19 complexed to AMA1 from P. vivax and P. falciparum shows that the monoclonal antibody recognises a discontinuous epitope located on domain III of the ectoplasmic region, the major component being a loop containing a cystine knot. The structures provide a basis for understanding the cross-reactivity. Antibody contacts are made mainly to main-chain and invariant side-chain atoms of AMA1; contact antigen residues that differ in sequence are located at the periphery of the antigen-binding site and can be accommodated at the interface between the two components of the complex. The implications for AMA1 vaccine development are discussed.

Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis, is transmitted through tick bite. Lyme borreliosis evolves in two stages: a primary red skin lesion called erythema migrans; later on, invasive bacteria disseminate to distant sites inducing secondary manifestations (neuropathies, arthritis, carditis, late skin disorders). It has been previously suggested that the ospC gene could be associated with invasiveness in humans depending on its sequence. Here, we confirm the pattern of invasiveness, according to B. burgdorferi sensu stricto (B. b. ss) ospC group, using the mouse as an experimental host of B. b. ss. As it has been shown that the host plasminogen activation system is used by B. burgdorferi to disseminate throughout the host, we studied the interaction of plasminogen with OspC proteins from invasive and non-invasive groups of B. b. ss. Using two methods, ELISA and surface plasmon resonance, we demonstrate that indeed OspC is a plasminogen-binding protein. Moreover, significant differences in binding affinity for plasminogen are correlated with different invasiveness patterns in mice. These results suggest that the correlation between ospC polymorphism and Borrelia invasiveness in humans is linked, at least in part, to differences in OspC affinity for plasminogen.

The involvement of serum anti-ovarian autoantibodies (AOA) in ovarian pathology still remains controversial. In some cases of clinically patent ovarian failure, there seems to be a causal relationship between AOA and the ovarian disease. In patients with various organ-specific or systemic autoimmune diseases, or with unexplained, repeated reproductive failure, but otherwise normal ovarian function, it is even more difficult to determine the significance of AOA for several reasons: i) AOA recognize many different antigenic targets in the ovary ii) the antiovarian response may be transient or variable with time iii) the presence of AOA does not imply their aetiopathogenic role in the disease. The present paper reviews the clinical significance of AOA based on their ovarian targets as far as they have been identified until now.

Recurrent unexplained abortions are defined as at least two successive abortions during the first trimester of pregnancy. Implication of autoimmunity processes is now widely recognized. The list of biological assays proposed in recurrent abortions is inspired from immunological exploration of systemic lupus erythematosus in which pregnancy usually induces high risk for the conception product. Other assays derive from immunological hypotheses explaining the tolerance paradox of pregnancy, but many have not yet been established and will still require clinical research protocols.

Objectives: To assess anti-ovarian antibodies (AOA) in serum samples at various times of in vitro fertilization (IVF) attempts to determine whether ovarian stimulation could result in the production of such autoantibodies in women., Patients and Methods: Prospective study on 134 patients and 138 IVF cycles using a classical long protocol. For each attempt, four serum samples were obtained, respectively, at the onset of downrelation (S1), end of downregulation (S13), after 7 days of follicular stimulation (S21) and the day of follicular puncture (SP). Five hundred and fifty two samples were tested with an enzyme-linked immunosorbent assay for three isotypes (IgG, IgA, IgM) of AOA., Results: In the whole group, mean concentrations of AOA for each isotype were compared group by group: S1-S13, S1-S21, S1-SP, S13-S21, S13-SP, S21-SP. Not any significant difference was observed whatever the isotype considered., Discussion and Conclusion: This study shows the absence of influence of endogenous or exogenous ovarian stimulation by gonadotropins on anti-ovarian autoimmunity.

The ovary can be the target of an autoimmune disease involving many different autoantigens. The clinical feature of this disease often results in premature ovarian failure or infertility and may be either isolated or associated with other autoimmune pathologies, especially with adrenal autoimmunity. The diagnosis of an autoimmune mechanism relies on the presence of anti-ovarian antibodies, whose prevalence is quite variable according to the different methods used to detect them, and to the different stages of the disease. In addition, their clinical significance is not always clear, as to their pathologic or epiphenomenal nature. However, the study of these autoantibodies has led to the identification of some of their antigenic targets which have to be known for a better understanding of the pathologic mechanisms involved. This paper reviews anti-steroid producing cells, anti-gonadotrophin receptor, anti-gonadotrophin, anti-corpus luteum, anti-zona pellucida and anti-oocyte antibodies.

Two novel acceptors for ammodytoxin C, a presynaptically neurotoxic phospholipase A(2) from snake venom, have been purified from porcine cerebral cortex by a toxin-affinity-based procedure. Using tandem mass spectrometry, the isolated acceptors were identified as 14-3-3 gamma and epsilon isoforms, highly conserved cytoplasmic proteins involved in the regulation of numerous physiological processes. The interaction between ammodytoxin C and 14-3-3 proteins is direct and not mediated by calmodulin, a high-affinity acceptor for both ammodytoxin C and 14-3-3 proteins, as demonstrated in pull-down experiments and by surface plasmon resonance. The latter technique gave an apparent dissociation constant of 1.0+/-0.2 microM for the interaction between chip-immobilized 14-3-3 and ammodytoxin C. 14-3-3 usually interacts with proteins through specific phospho-Ser/Thr motifs. Ammodytoxin C is not a phospho-protein, therefore the interaction must occur through a non-phosphorylated binding site, most probably the KEESEK sequence at its C-terminal end. The interaction we describe suggests an explanation for the pathophysiological effects evoked by some secreted phospholipases A(2), such as the inhibition of protein phosphorylation, of terminal ion currents, and of neurotransmission, as well as the initiation of neuronal cell death, all processes regulated by 14-3-3 proteins.

The purpose of this study was to identify autoantigens contained in human ovary extracts. Serum samples from 36 infertile women with anti-ovary antibodies as detected with an ELISA technique were tested in Western blot against human ovary extracts. A reactive protein with a molecular mass matching that of the FSH was detected in 34 cases. These serum samples also reacted strongly in Western blot and ELISA with purified FSH and, in immunofluorescence, with pituitary cells. Using the Pepscan approach, with overlapping peptides matching the amino acid sequence of the human FSH beta-chain, several immunoreactive regions were evidenced. The 78-93 amino acid sequence of the human FSH beta-chain appeared as one of the major epitopes. Synthetic peptides of this region were prepared and demonstrated to react with human serum samples from women with anti-ovary antibodies. These data demonstrate that FSH can be an autoantigen, recognized by autoantibodies associated with infertility., ((c)2001 Elsevier Science.)

Leukocyte enzymatic activities are important in non-specific protection against bacterial infections, but traditional methods for the detection of intracellular enzymatic activities rely on cumbersome and complex assays. The development of specific substrates, which become fluorescent upon degradation of the biomolecule after its passive entry into intact cells, permits a simplified evaluation of leukocyte enzymatic activities. We have used this method to assess intracellular elastase, collagenase and cathepsin D activities of peripheral blood leukocytes using flow cytometry in a series of HIV patients and healthy controls. Monocytes displayed the highest enzymatic activities for the three proteases tested. In HIV-infected patients, the collagenase and cathepsin D activities of monocytes were significantly lower, whereas the elastase and cathepsin D activities of polymorphonuclear cells were elevated. Slightly higher elastase activity was detected in the lymphocytes of patients. This study demonstrates the feasibility of this new method for the study of intracytoplasmic enzymatic activities. Significant variations were observed in the peripheral blood of HIV-infected patients and different patterns were especially evident in monocytes and polymorphonuclear cells.

A Ser48 phospholipase A2-homologue, ammodytin L, which is myotoxic in mammals and devoid of any phospholipase A2 activity, completely inhibits the specific binding of the neurotoxic phospholipase A2, ammodytoxin C, to fish presynaptic membranes from Torpedo marmorata electric organ. In cross-linking experiments, 125I-ammodytin L labels the same membrane proteins as 125I-ammodytoxin C (70, 38.5-57.4 and 19.7 kDa). The formation of these adducts is completely prevented by the presence of ammodytoxin C but not of a non-toxic phospholipase A2, ammodytin I2. A chimeric phospholipase A2, constructed by associating the N-terminal half of ammodytoxin to the C-terminal half of ammodytin L, possesses a low, but significant phospholipase A2 activity, however it is not toxic to mice, probably due to abolition of the specific neuronal acceptor binding in mammals. Nevertheless, the chimeric phospholipase A2 is able to interact with the ammodytoxin acceptor in Torpedo marmorata electric organ. The existence of neuronal acceptors for ammodytin L and for the chimeric phospholipase A2 suggests that they may act as neurotoxins in fish. As ammodytin L does not possess any enzymatic activity it, therefore, appears to be an excellent tool to investigate the mechanism of action of beta-neurotoxins independently of their phospholipase A2 activity.

The binding of bovine plasminogen to whole casein, alpha s-casein, beta-casein, and kappa-casein is responsible for the progressive proteolysis of milk and dairy products. A sensitive and accurate microparticle-enhanced nephelometric immunoassay was developed to measure free plasminogen after interaction between bovine plasminogen and caseins and the quantitative parameters of plasminogen/casein binding were established. Two classes of binding sites for plasminogen were found in this study on each of the investigated caseins. Their dissociation constants (Kd) were determined by varying the plasminogen concentration at pH 6.6 and performing Scatchard analysis. The two binding sites appeared to be one of high affinity (Kd = 32 nM) and the other of lower affinity (Kd > 370 nM). The number of both binding sites per casein monomer was low (0.04 to 0.53). The great propensity of casein monomers to self-associate in homopolymers where plasminogen binding sites could be hidden and in copolymers present in bovine milk in the form of whole casein micelles accounts for calculated binding sites < 1 per monomer.

Immunoglobulin kappa light chains are predominant in normal human serum and a kappa/lambda ratio of 1.7 to 2 has been reported. However, little is known of the partition of light chains in secretions. The levels of IgA, kappa and lambda were assayed by nephelometry in a series of secretions and in normal human serum. Although kappa chains remained predominant, the different secretions studied could be classified according to their kappa/lambda ratio. In saliva (P < 0.001), nasal fluid (P = 0.01) and tears (P = 0.04) the kappa/lambda ratio was significantly lower than in serum. Conversely, higher kappa/lambda ratios were obtained in gastric juice (P = 0.005) and hepatic bile (P = 0.004) and no significant difference was noted between serum and gall bladder bile (P = 0.62). The lower ratios were all observed in fluids produced by glands surrounded by lymphoid tissue included in the mucosae-associated lymphoid tissue. These data strengthen previous observations that suggest a preferential production of lambda chains in human mucosae.

Expression of the T-cell receptor (TCR) was investigated on peripheral lymphocytes in 270 samples from HIV+ patients at different stages of infection. TCR is composed either of an alpha and a beta chain, or, in a smaller subset of T-cells, of a gamma and a delta chain, closely associated with CD3. The numbers and percentages of positive cells were established using monoclonals to the alpha and delta chains of TCR. The values of alpha-TCR positive cells were constantly lower than those observed for CD3, with a mean of 53% (+/- 19%) versus 66% (+/- 17) respectively for asymptomatic patients or patients with persistent generalized lymphadenopathy, and of 36% (+/- 19) versus 46% (+/- 21) for patients with AIDS disease. There was no compensatory increase in the number of cells expressing delta-TCR. These data demonstrate a new alteration of the immune system in HIV infection, which appears to occur early in this disease.

This investigation was designed to investigate mechanisms underlying oral immunization in humans after ingestion of the ribosomal vaccine D53. Immunofluorescence and ELISA (Enzyme-Linked ImmunoSorbent Assay) spot techniques were used for peripheral blood studies. The first part of the investigation was a double-blind placebo-controlled study of 12 healthy volunteers; counts of cells containing immunoglobulins and cells producing specific antibodies were higher in the individuals given the oral ribosomal vaccine than in the placebo-treated controls. In the second part of the investigation, analysis of the kinetics of apparition of the immunoglobulin-containing and specific antibody-producing cells suggested prompt stimulation of Peyer patch B lymphocytes following ingestion of the vaccine. Lastly, a study of 5 children given the vaccine on a long-term basis demonstrated increased counts of both above-described cell types after one month treatment.

The prognosis of cancers is conditioned by tumoral extension. We report a case of a squamous carcinoma of the vulva where pathological examination had been at fault. An immunohistological study performed with monoclonal antibodies revealed a lymph node micro-metastasis. This case emphasizes the importance of estimating the tumoral extension by simultaneous pathological and immunological examinations.

In 6 cases of eclampsia in the course of pre and post-partum, we could observe neurological disorders associated with acute pulmonary oedema with acute respiratory distress occurring 5 to 72 hours after the first convulsive crisis. Hemodynamic check-up provided various results: 3 cases corresponded to A.P.O resulting from a lesion, with normal capillary pressure. In 3 other cases, there was hemodynamic oedema (overloading with high flow and hypervolemia in one case, myocardial incompetence with hypovolemia in an other case revealed by test filling in a third case). There were clinical signs of left ventricular failure in 4 case. Post-mortem investigations (5 cases) revealed unimportant ultrastructural alterations of myocardium only in 2 cases. Pulmonary histopathological investigations (5 cases) were the investigations carried out in case of oedema resulting from lesions with interstitial and alveolar oedema, hyaline membranes, alteration of pneumocytes, and intra-capillary thrombi. Mendelson's syndrome which was always discussed could be eliminated. The syndrome of respiratory distress was certainly connected with more or less generalized microcirculatory disorders (microembolism with hyperpermeability) connected with hemostasis disorders and cerebral manifestations.

Three children with IgA and IgE deficiency and T-cell defects (two related patients with ataxia telangiectasia and one with common variable immune deficiency) were treated with synthetic serum thymic factor (FTS) intravenously. A reduction in frequency and severity of infection was noted concomitantly with improvement in cell-mediated-immunity tests. Serum IgA, which was absent in two patients, appeared within 4 weeks of treatment and increased significantly in the third patient. Specific antibodies against vaccination antigens appeared for the first time or increased to titres higher than ever before. In two patients, transient interruption of FTS administration was followed by a regression of the immunological improvement, but this disappeared after the treatment was started again.

This study analyzes the outcome of human normal and hyperfunctioning thyroid tissue transplanted to the nude mouse. Thyroid fragments from 7 patients with Graves' disease were transplanted to nude mice (nu/nu). Before surgery, the patients had been treated with propranolol and iodine; none had received antithyroid therapy. The transplants were removed on the 12th day following transplantation and were studied by light microscopy and autohistoradiography. At this time, all immunologic disorders found on the operative samples had disappeared, and the tissue had lost its hyperfunctioning characteristics. In contrast, transplants from toxic adenoma remained hyperfunctioning, with elevated serum T3 and T4 levels. Similarly, transplants from normal thyroid tissue remained unchanged, and serum T3 and T4 levels remained within the normal range, as if under the influence of the hypothalamic and pituitary regulation of the mice. These findings emphasize the role of the extrathyroid immunologic environment in the regulation of Graves' disease, whereas toxic adenoma remains autonomous.

Organ- and non organ-specific autoantibodies can be detected in patients with AITD but large comparative studies have seldom been performed. This study evaluated the prevalence of anti-thyroid, -smooth muscle, -mitochondria, -parietal gastric cells, -salivary duct, -nuclear and -ds DNA autoantibodies assayed by indirect immunofluorescence in 224 patients with Graves' disease or Hashimoto's thyroiditis. Results evidenced a high prevalence of antinuclear antibodies, mostly of non homogenous fluorescence in Graves' (63.1%) and Hashimoto's patients (65.5%), as well as for antisalivary duct antibodies (55.2 and 75%). No positive anti-ds DNA were noticed. No correlation was found between antithyroid antibodies and the others. Different hypothesis could explain this observation which favours a general dysregulation of the autoimmune system.

Pulse polarography with anodic stripping has shown the presence of very high levels (2 005 microgram/kg and 6 760 microgram/kg) of bismuth in bone of two patients treated with bismuth, one parenterally and the other orally. The presence of high levels of bismuth in bone of these patients must be considered in the etiology of their athropathies. Pulse polarography with anodic stripping now permits very precise measurement of bismuth impregnating bones.

The aim of this experiment was to determine the inflammatory effect of aluminium phosphate on the rat paw and to compare it with those of carrageenan, calcium hydrogen phosphate dihydrate and natural diamond powder. At the probability threshold of the various tests used there was a significant increase in volume of the treated paw relative to the control paw for all the substances at all times, except for the two concentrations of diamond (effect no longer significant from 30 min on), of calcium phosphate (not significant from 2 h), and of aluminium phosphate (not significant from 24 h). The effects were not significantly different between diamond and calcium phosphate (both concentrations). The effects of aluminium phosphate were significantly different from those of the two until at least 2 h after the injection ; there was no significant difference between the two doses of this substance. The kinetics of the effects produced by carrageenan differed from the kinetics of the other materials, its effects were not significantly different from those produced by aluminium phosphate until 2 h and later. The inflammatory effect that we have demonstrated in this study is added information suggesting that in addition to apatite, calcium pyrophosphate dihydrate, and sodium monourate, aluminium compounds can play a role in the unexpected appearance of inflammatory manifestations in haemodialysed patients with chronic renal insufficiency treated with aluminium gels.