Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

Effect of Nintedanib in Patients with Progressive Pulmonary Fibrosis in Subgroups with Differing Baseline Characteristics.

INTRODUCTION: In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced vital capacity (FVC; mL/year) over 52 weeks compared with placebo. We assessed the efficacy of nintedanib across subgroups in the INBUILD trial by baseline characteristics. METHODS: We assessed the rate of decline in FVC over 52 weeks and time to progression of interstitial lung disease (ILD) (absolute decline from baseline in FVC % predicted > 10%) or death over the whole trial in subgroups based on sex, age, race, body mass index (BMI), time since diagnosis of ILD, FVC % predicted, diffusing capacity of the lungs for carbon monoxide (DLco) % predicted, composite physiologic index (CPI), GAP (gender, age, lung physiology) stage, use of anti-acid therapy and use of disease-modifying antirheumatic drugs (DMARDs) at baseline. RESULTS: The effect of nintedanib versus placebo on reducing the rate of decline in FVC over 52 weeks was consistent across the subgroups by baseline characteristics analysed. Interaction p values did not indicate heterogeneity in the treatment effect between these subgroups (p > 0.05). Over the whole trial (median follow-up time ∼19 months), progression of ILD or death occurred in similar or lower proportions of patients treated with nintedanib than placebo across the subgroups analysed, with no heterogeneity detected between the subgroups. CONCLUSIONS: In the INBUILD trial, no heterogeneity was detected in the effect of nintedanib on reducing the rate of ILD progression across subgroups based on demographics, ILD severity or use of anti-acid therapy or DMARDs. These data support the use of nintedanib as a treatment for progressive pulmonary fibrosis. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02999178.

Toxicological evaluation of zidovudine and novel chalcogen derivatives in Drosophila melanogaster.

Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 µM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno-phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p-methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates.

Polimorfismos en el gen FRMD4A se asocian a riesgo de enfermedad pulmonar obstructiva crónica en población latinoamericana / Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population

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[Translated article] Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population / Polimorfismos en el gen FRMD4A se asocian a riesgo de enfermedad pulmonar obstructiva crónica en población latinoamericana

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Specific miRNA Profile in Chronic Obstructive Pulmonary Disease Related to Biomass Smoke Exposure / Perfil específico de miRNAs en enfermedad pulmonar obstructiva crónica asociada a exposición a humo de biomasa

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Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.

INTRODUCTION: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. OBJECTIVES: The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. METHODS: The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. RESULTS: This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. CONCLUSION: The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas  classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population / Los alelos de HLA-DRB1 se asocian con la EPOC en una población latinoamericana mestiza

Introduction: While the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.Methods: COPD patients (n=214) and age-matched controls (n=193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.Results: CODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p=0.04, OR=2.07). HLA-DRB1*01:02 was also significantly associated with FEV1 (p=0.04) and oxygen saturation (p=0.02), and the FEV1/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p=9×10−3).Conclusion: We report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD. (AU)

Introducción: Si bien los mecanismos moleculares de la patogénesis de la EPOC siguen sin ser claramente conocidos, cada vez existe más información que respalda que la autoinmunidad tiene un papel clave. Aunque los alelos de los antígenos leucocitarios humanos (HLA) se han asociado repetidamente con procesos autoinmunes, la relación entre los HLA y la EPOC permanece en gran parte inexplorada, especialmente en las poblaciones latinoamericanas (LA). En consecuencia, este estudio tuvo como objetivo investigar la presencia de los alelos de HLA de clase I y II en pacientes con EPOC y controles sanos en una población LA mestiza.Métodos: Se analizó el genotipo de pacientes con EPOC (n=214) y controles de la misma edad (n=193) utilizando el Illumina Infinium Global Screening Array. Los alelos clásicos de los HLA se imputaron usando la imputación del genotipo HLA con empaquetamiento de atributos (HIBAG, por sus siglas en inglés) y el panel de referencia hispano. Finalmente, la distribución de los alelos HLA-DRB1 se reexaminó en 510 voluntarios no emparentados reclutados al azar.Resultados: Los pacientes con EPOC mostraron una mayor frecuencia de alelos HLA-DRB1*01:02 (6,54%) que los controles sanos (3,27%; p=0,04; OR=2,07). El HLA-DRB1*01:02 también se asoció significativamente con el FEV1 (p=0,04) y la saturación de oxígeno (p=0,02), y la relación FEV1/FVC fue mayor en los pacientes con HLA-DRB1*15:01 (p=9×10-3).Conclusión: Comunicamos una asociación entre los alelos HLA-DRB1, el riesgo de la EPOC y los parámetros de la función pulmonar por primera vez en latinoamericanos. Dado que la variabilidad genética de HLA-DRB1 se relaciona con la respuesta autoinmune individual, estos resultados respaldan el papel de la autoinmunidad en la patogénesis de la EPOC. (AU)

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population.

INTRODUCTION: While the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry. METHODS: COPD patients (n=214) and age-matched controls (n=193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers. RESULTS: CODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p=0.04, OR=2.07). HLA-DRB1*01:02 was also significantly associated with FEV1 (p=0.04) and oxygen saturation (p=0.02), and the FEV1/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p=9×10-3). CONCLUSION: We report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.

Amerindian Ancestry Influences Genetic Susceptibility to Chronic Obstructive Pulmonary Disease.

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5×10-4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10-3 to 3.77×10-8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.

PRDM15 Is Associated with Risk of Chronic Obstructive Pulmonary Disease in a Rural Population in Chile.

BACKGROUND: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with ∼1% of Latin American ancestry. OBJECTIVE: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. METHOD: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. RESULTS: PRDM15 rs1054761 C allele (p = 2.22 × 10-7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10-6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. CONCLUSION: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.

Role of imaging in progressive-fibrosing interstitial lung diseases.

Imaging techniques are an essential component of the diagnostic process for interstitial lung diseases (ILDs). Chest radiography is frequently the initial indicator of an ILD, and comparison of radiographs taken at different time points can show the rate of disease progression. However, radiography provides only limited specificity and sensitivity and is primarily used to rule out other diseases, such as left heart failure. High-resolution computed tomography (HRCT) is a more sensitive method and is considered central in the diagnosis of ILDs. Abnormalities observed on HRCT can help identify specific ILDs. HRCT also can be used to evaluate the patient's prognosis, while disease progression can be assessed through serial imaging. Other imaging techniques such as positron emission tomography-computed tomography and magnetic resonance imaging have been investigated, but they are not commonly used to assess patients with ILDs. Disease severity may potentially be estimated using quantitative methods, as well as visual analysis of images. For example, comprehensive assessment of disease staging and progression in patients with ILDs requires visual analysis of pulmonary features that can be performed in parallel with quantitative analysis of the extent of fibrosis. New approaches to image analysis, including the application of machine learning, are being developed.

Safety profile of AZT derivatives: Organoselenium moieties confer different cytotoxic responses in fresh human erythrocytes during in vitro exposures.

INTRODUCTION: The incorporation of selenium in the structure of nucleosides is a promising strategy to develop novel therapeutic molecules. OBJECTIVE: To assess the toxic effects of three AZT derivatives containing organoselenium moieties on human erythrocytes. METHODOLOGY: Freshly human erythrocytes were acutely treated with AZT and selenium derivatives SZ1 (chlorophenylseleno), SZ2 (phenylseleno) and SZ3 (methylphenylseleno) at concentrations ranging from 10 to 500 µM. Afterwards, parameters related to membrane damage, redox dyshomeostasis and eryptosis were determined in the cells. RESULTS: The effects of AZT and derivatives toward erythrocytes differed considerably. Overall, the SZ3 exhibited similar effect profiles to the prototypal AZT, without causing cytotoxicity. Contrary, the derivative SZ1 induced hemolysis and increased the membrane fragility of cells. Reactive species generation, lipid peroxidation and thiol depletion were also substantially increased in cells after exposure to SZ1. δ-ALA-D and Na+/K+-ATPase activities were inhibited by derivatives SZ1 and SZ2. Additionally, both derivatives caused eryptosis, promoting cell shrinkage and translocation of phosphatidylserine at the membrane surface. The size and granularity of erythrocytes were not modified by any compound. CONCLUSION: The insertion of either chlorophenylseleno or, in a certain way, phenylseleno moietes in the structure of AZT molecule was harmful to erythrocytes and this effect seems to involve a pro-oxidant activity. This was not true for the derivative encompassing methylphenylseleno portion, making it a promising candidate for pharmacological studies.

Diversity Driven Decoration and Ligation of Fullerene by Ugi and Passerini Multicomponent Reactions.

Aiming at providing an efficient and versatile method for the diversity-oriented decoration and ligation of fullerenes, we report the first C60 derivatization strategy based on isocyanide-multicomponent reactions (I-MCRs). The approach comprises the use of Passerini and Ugi reactions for assembling pseudo-peptidic scaffolds (i.e., N-alkylated and depsipeptides, peptoids) on carboxylic acid-functionalized fullerenes. The method showed wide substrate scope for the oxo and isocyanide components, albeit the Ugi reaction proved efficient only for aromatic amines. The approach was successfully employed for the ligation of oligopeptides and polyethyleneglycol chains (PEG) to C60 , as well as for the construction of bis-antennary as well as PEG-tethered dimeric fullerenes. The quantum yields for the formation of 1 O2 was remarkable for the selected compounds analyzed.

Chalcogenozidovudine Derivatives With Antitumor Activity: Comparative Toxicities in Cultured Human Mononuclear Cells.

Considering a novel series of zidovudine (AZT) derivatives encompassing selenoaryl moieties promising candidates as therapeutics, we examined the toxicities elicited by AZT and derivatives 5'-(4-Chlorophenylseleno)zidovudine (SZ1); 5'-(Phenylseleno)zidovudine (SZ2); and 5'-(4-Methylphenylseleno)zidovudine (SZ3) in healthy cells and in mice. Resting and stimulated cultured human peripheral blood mononuclear cells (PBMCs) were treated with the compounds at concentrations ranging from 10 to 200 µM for 24 and/or 72 h. Adult mice received a single injection of compounds (100 µmol/kg, s.c.) and 72 h after administration, hepatic/renal biomarkers were analyzed. Resting and stimulated PBMCs exposed to SZ1 displayed loss of viability, increased reactive species production, disruption in cell cycle, apoptosis and increased transcript levels and production of pro-inflammatory cytokines. In a mild way, most of these effects were also induced by SZ2. AZT and SZ3 did not cause significant toxicity towards resting PBMCs. Differently, both compounds elicited apoptosis and S phase arrest in stimulated cells. AZT and derivatives administration did not change the body weight and plasma biochemical markers in mice. However, the absolute weight and organ-to-body weight ratio of liver, kidneys and spleen were altered in AZT, SZ1-, and SZ2-treated mice. Our results highlighted the involvement of derivatives SZ1 and SZ2 in redox and immunological dyshomeostasis leading to activation of apoptotic signaling pathways in healthy cells under different division phases. On the other hand, the derivative SZ3 emerged as a promising candidate for further viral infection/antitumor studies as a new effective therapy with low toxicity for immune cells and after acute in vivo treatment.

New organochalcogen multitarget drug: synthesis and antioxidant and antitumoral activities of chalcogenozidovudine derivatives.

In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.

Comparative analysis of different joining techniques to improve the passive fit of cobalt-chromium superstructures.

STATEMENT OF PROBLEM: The influence of different joining techniques on passive fit at the interface structure/abutment of cobalt-chromium (Co-Cr) superstructures has not yet been clearly established. PURPOSE: The purpose of this study was to compare 3 different techniques of joining Co-Cr superstructures by measuring the resulting marginal misfit in a simulated prosthetic assembly. MATERIAL AND METHODS: A specially designed metal model was used for casting, sectioning, joining, and measuring marginal misfit. Forty-five cast bar-type superstructures were fabricated in a Co-Cr alloy and randomly assigned by drawing lots to 3 groups (n=15) according to the joining method used: conventional gas-torch brazing (G-TB), laser welding (LW), and tungsten inert gas welding (TIG). Joined specimens were assembled onto abutment analogs in the metal model with the 1-screw method. The resulting marginal misfit was measured with scanning electron microscopy (SEM) at 3 different points: distal (D), central (C), and mesial (M) along the buccal aspect of both abutments: A (tightened) and B (without screw). The Levene test was used to evaluate variance homogeneity and then the Welsch ANOVA for heteroscedastic data (α=.05). RESULTS: Significant differences were found on abutment A between groups G-TB and LW (P=.013) measured mesially and between groups G-TB and TIG (P=.037) measured centrally. On abutment B, significant differences were found between groups G-TB and LW (P<.001) and groups LW and TIG (P<.001) measured mesially; groups G-TB and TIG (P=.007) measured distally; and groups G-TB and TIG (P=.001) and LW and TIG (P=.007) measured centrally. CONCLUSIONS: The method used for joining Co-Cr prosthetic structures had an influence on the level of resulting passive fit. Structures joined by the tungsten inert gas method produced better mean results than did the brazing or laser method.