B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study.

OBJECTIVES: Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. PATIENTS AND METHODS: Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. RESULTS: The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. CONCLUSIONS: This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease.

Seronegative conversion after incomplete benznidazole treatment in chronic Chagas disease.

In 12-18% of adult patients, treatment with benznidazole for chronic Chagas disease has to be discontinued because of side-effects. We identified and analysed a cohort of 81 adult patients with three positive tests for Trypanosoma cruzi infection and serological monitoring following incomplete treatment with benznidazole for a median of 10 days. Twenty percent of these patients (16/81) met the criteria of cure, showing that the optimal schedule of benznidazole administration remains to be determined.

Value of echocardiography for diagnosis and prognosis of chronic Chagas disease cardiomyopathy without heart failure.

OBJECTIVES: To establish the usefulness of echocardiography for the clinical classification of patients with Chagas disease and to determine the predictors of mortality and clinical events. METHODS: 849 patients with chronic Chagas disease with a mean follow up of 9.9 years were studied. On admission, ECG, chest radiograph, and two dimensional echocardiogram were obtained from all patients. Clinical events were defined as new ECG abnormalities, change in clinical status resulting in transfer to another group, and death. Morphologically characterised segmental lesions were also seen in 12 patients on a second harmonic echocardiogram with intravenous contrast agent. Univariate and multivariate analysis for clinical events and mortality were performed. SETTING: Community of San Martín, Buenos Aires, Argentina. RESULTS: Change in clinical group (68 of 833 survivors v 15 of 16 who died, p < 0.001), left ventricular systolic dimension (mean (SD) 3.06 (0.72) cm v 4.71 (0.90) cm, p < 0.0001), and ejection fraction (mean (SD) 0.67 (0.11)% v 0.42 (0.17)%, p < 0.0001) were found to be the only predictors of mortality. ECG abnormalities related to the disease (in 220 of 699 patients with no clinical event v 98 of 150 patients with a clinical event, p < 0.0001), left ventricular diastolic dimension (mean (SD) 4.88 (0.54) cm v 5.44 (0.83) cm, p < 0.0001), left ventricular systolic dimension (mean (SD) 2.98 (0.62) cm v 3.64 (1.03) cm, p < 0.0001), and ejection fraction (mean (SD) 0.68 (0.10)% v 0.60 (0.16)%, p < 0.0001) were predictors of clinical events. Segmental lesions were observed in 211 of 849 patients (25%). Segmental lesions were seen in 66 (13%) and systolic dysfunction was seen in four of 505 (0.8%) patients with normal ECG. Significant differences were found between the groups of patients (group 0: reactive serology and normal ECG and chest radiography without cardiac enlargement and no signs of heart failure; group 1: reactive serology and abnormal ECG and chest radiography without cardiac enlargement; group 2: reactive serology and abnormal ECG and chest radiography with cardiac enlargement and no signs of heart failure). CONCLUSION: Echocardiography was useful both to characterise and to determine the prognosis of patients with chronic Chagas disease without heart failure.

[The characteristics and properties of calcium phosphates in biomaterial formulations used in dentistry. 1]. / Caratteristiche e proprietà di alcuni fosfati di calcio presenti nella formulazione di biomateriali impiegati in odontostomatologia. Nota 1.

In this work we present the features and the properties of natural and synthetic apatites, which we use in an experimental study of various commercial products composed by calcium phosphate. After having considered the general concepts of biomaterials and biocompatibility, we describe non biological tests used for the characterization of these products. Biomaterials used in this study are: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2 Osprogel, Bio-oss, Biostite, Osprovit, Merck Hydroxiapatite. Tests used are: X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric and thermodifferential analysis (TG, DTG, DTA), scanner-ing electron microscopy (SEM) morphological analysis. Last but not least, we underline the particular features of these tests whose interpretation allows a more precise definition of the bioactivity of a biocompatible material.

[The X-ray fluorescence (XRF) spectrometry of biomaterials used in dentistry. 2]. / Analisi in spettrometria per fluorescenza di raggi X (XRF) di biomateriali utilizzati in odontostomatologia. Nota 2.

In this work we analyze the following biomaterial: biomaterials used in this study are: reabsorbable Dac Blu, non reabsorbable Dac Blu, non reabsorbable atomized Dac Blu, non reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxiapatite. The quantitative XRF analysis was performed by a Philips PW 1480 with Rh tube. This research, besides underlining the possibility of applying the XRF method to the analysis of biomaterials. This study, shows the facility and the rapidity in the preparation of samples and standards in the form of tablets to undergo the analysis: furthermore the study shows the possibility of verify the analysis on the same sample in the future, because the tablet if well conserved, does not deteriorate. We can also verify a good analytic accuracy both for the principal elements (Ca, P) and for trace elements. The analyses show a moderate variability in the Ca/P ratio in the hydroxylapatites, and a greater variability in the secondary and trace elements.

[The specific characteristics determined by nonbiological tests of mineral-based biomaterials used in dentistry. 7]. / Considerazioni sulle specifiche ottenute da test non biologici relative a biomateriali a base minerale utilizzati in odontostomatologia. Nota 7.

In this work we relate about the results coming from crystallographic, physical and mineral tests taken on following biomaterials used in odontostomatology: reabsorbable Dac Blu, non reabsorbable Dac Blu, not reabsorbable atomized Dac Blu, not reabsorbable thin Dac Blu, reabsorbable Biocoral 450, Calcitite 2040-12, Orthogel, Apagen, BTF 65, Calcitite 4060-2, Osprogel, Bio-Oss, Biostite, Osprovit, Merck Hydroxiapatite. The data were obtained using the following tests: XRF, XRD, FTIR, TG, DTG, DTA, SEM. The results, although taken on few samples, showed that these biomaterials present a variability in some features, which can define the structural functionality.

A new material with theoretical osteoinductive properties: experimental evaluation.

An intensive research for bone substitutes has been in progress for several decades in order to find a new ideal material for bone replacement. In the present study the Authors report some data on a new developed material in comparison with synthetic hydroxyapatite. The new material was characterised by means of a crystallographic spectroscopic and chemical study. An in vitro test was also performed using murine fibroblasts. The results of this preliminary study showed that the sintered material has an and beta-tricalcium-phosphate (TCP) lattice depending on thermal treatment in accordance with literature data. Moreover, it showed a high level of biocompatibility. Though it is still in an investigation stage, perhaps this biomaterial is a highly reactive and unstable compound that could interact with CO2 and H2O.

Scanning electron microscopy, chemical and histologic analysis in human periarthritic shoulder biopsy.

In the present study biopsies were analyzed, taken from the left shoulder of a patient who, according to the radiological diagnosis, was suffering from calcific periarthritis. In both optical and electronic microscopy the mineralogical observations showed crystalline aggregations, while the chemical analysis, carried out with an Edax EDS spectrophotometer, confirmed the presence of Ca and P in them, in the ratio typical of biological apatites. The histological observations clearly indicate a change in the metabolism of the tissues present. In the samples observed the damage to the muscular tissues is easily seen while the connective tissue, though apparently less compromised, shows the presence of numerous calcifications whose damage cannot be revealed solely through histologic observations. The authors, linking the structural histologic alterations observed to the presence of hydroxyapatite granules as well as to the patient's painful symptoms, believe all these observations are the result of a chronic process.

Osteoporosis by ovariectomy: calcitonin effect in an experimental model on the rat.

The authors evaluate the efficacy of the aminosuberic derivative of eel calcitonin (eCT) in preventing post-ovariectomy osteoporosis in adult rats. The drug is administered in a dose of 0.5 U.I./day for four months starting from the moment of the ovariectomy. The results show that the treatment is efficacious in preventing bone mass loss due to ovariectomy and that the action of the drug does not bring about alterations in the normal crystalline structure of the bone.

Thermodynamical aspects of the polymerization reaction of PMMA cement mixed with phosphatic mineral phases.

The main problem related to the use of polymeric cement in orthopaedics is the high temperature reached during the polymerization, causing necrosis. This paper reports a thermodynamical study of the polymerization reaction of an acrylic cement mixed with powdered phosphatic phases. In particular, mixing of alpha-tricalciumphosphate, beta-tricalciumphosphate and hydroxyapatite was proposed. Important preliminary results indicated that amounts of about 66% by weight of alpha-tricalciumphosphate reduced the polymerization temperature to about 58 degrees C in respect to 100 degrees C of pure acrylic cement. In addition, a special chamber was designed and realized to monitor the temperature variations involved during the polymerization reaction of the different mixtures.

Chemistry and structure of a new canal sealer showing a dynamical behaviour.

The complete apical seal without percolation and transit of bacteria and their products along the wall of the endodontic canal is the fundamental condition to obtain a lasting result of a correct endodontic therapy. The aim of this study was to characterize a new formulation cement (PROENDO, VEBAS, Italy) with characteristics totally different from the conventional ones. Finally, we can assert that an alloplastic material like PROENDO, which is the subject of this study, bio-compatible, osteo-inductive, non-toxic, with adhesive capacities, is able to quicken the phenomena of restoration and recovery after an endodontic operation.

Morphological and structural characteristics of the myopathic bone.

The aim of the present paper was to study the myopathic bone both from the morphological and structural viewpoints. To this end, samples from 8 patients affected by different neuromuscular diseases (DMD, SMA and CMD) have been examined. Thus, by SEM analysis a quantitative reduction of the trabeculae and an increase in porosity of the myopathic bone were found and also, by diffractometric analysis, the presence of pathologic crystalline phases (beta-TCP and beta-TCP-Mg).

Calcium oxalate smear layer: mineralogical and crystallographic study.

Different methods to reduce dentine hypersensitivity have been tested by means of oxalate treatments. Natural material (20 teeth) and commercial oxalates have been employed. As a result the dentinal tubules are filled by small crystals preventing dental disease. Permeability measurements have been performed in order to quantify results. The composition of the synthetic smear layer produced after oxalate treatment have been investigated by powder diffraction method suggesting calcium oxalate formation.

Influence of calcitonin treatment on the bone structure and mineral content in osteoarthritis.

8 femoral heads removed in 4 patients operated on by bilateral total hip replacement for osteoarthritis were evaluated. 3 patients were treated with Calcitonin between the first and the second operation. X-ray powder diffractometry analysis showed an improvement of bone crystallinity in the Calcitonin treated patients.

SEM and chemical micro-analysis in a failed total knee prosthesis.

Authors performed SEM and EDS analyses in a cemented removed knee prosthesis demonstrating the average values of mineral elements in the bone surrounding the prosthesis. The composition of the metallic prosthesis surface in different microareas was also studied.

Microleakage in composite resin restorations.

The aim of the present study was to evaluate the marginal microleakage of the newest generation of composite resin restorative materials. Class V restorations were prepared in human extracted teeth. Different combinations of restorative materials were used. All the materials tested showed marginal microleakage along the dentinal walls, suggesting that the adhesion value is not sufficient to counteract the composite shrinkage and to reduce the marginal space.

Influence of the fluoride ion in the stability of bone hydroxyapatite achieved in patients after the fluo-calcic therapy.

It has been proposed that fluoride ion might actively enter into the basic structural framework of the bone, within its main constituent, the hydroxyapatite (HA), by substituting systematically the OH- ion in the crystal chemical formula Ca5[(PO4)3OH]. Accurate compositional studies have become necessary in order to explain an eventual stabilizing effect. Loss in weight (TG) and chemical reaction (DTG) while varying the temperature have been carried out for the first time on specimens under normal conditions and after fluo-calcic treatment, in parallel with accurate chemical compositional determinations by atomic absorption analysis. Our investigation shows that the new structure present after treatment is mechanically stable and proves more resistant to osteolytic processes.

Dental composite resin porosity and effect on water absorption.

The aims of this study were: 1) to characterize the solubility and water absorption of different composite resins used as dental restorative materials; 2) to analyse their surface morphology using S.E.M. The resins tested were a mixture of glycidyl methacrylate (Bis-GMA) and TEGMA filled with silane-coated particles of inorganic fillers, and Bis-GMA and urethane resin. Cylindrical samples of composite resin were polymerized and stored in distilled water and weighed after different times. SEM analysis demonstrated voids and porous in several samples. The present study shows that dental restorative composite loose a small percentage of their components during storage time and that the type of resin, the nature of fillers and the methods of polymerization greatly influence water uptake and solubility of dental composite resin materials. These findings could explain the loss of anatomic form and the occlusal degradation of dental composites in "in vivo" conditions.