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1.
Trop Anim Health Prod ; 56(4): 132, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642253

ABSTRACT

The objectives of this study were to evaluate the influence of inbreeding on growth traits and body measurements, as well as on the estimation of genetic parameters and genetic trends in Guzerá cattle. Phenotypic records of 4,212 animals selected for postweaning weight from Guzerá Breeding Program of Advanced Beef Cattle Research Center were utilized. The pedigree file contained records from 7,213 animals born from 1928 to 2019. The traits analyzed were: birth weight (BW), weights adjusted to 210, 378 and 550 days of age (W210, W378 and W550, respectively), chest girth at 378 and 550 days of age (CG378 and CG550), scrotal circumference (SC), and hip height at 378 and 550 days of age (HH378 and H550). Linear regression was used to evaluate the effects of inbreeding on traits. Genetic parameters were obtained using models including or not the effect of inbreeding as a covariate. Inbreeding had negative effects (P ≤ 0.01) on BW (-0.09 kg), W378 (-2.86 kg), W550 (-2.95 kg), HH378 (-0.10 cm), and H550 (-0.29 cm). The lowest and highest heritability estimates were obtained for W210 (0.21 ± 0.07) and HH550 (0.57 ± 0.06), respectively. The genetic correlations were strong and positive between all traits, ranging from 0.44 ± 0.08 (SC x HH) to 0.99 ± 0.01 (W378 x W550). Spearman correlations between EBVs obtained with or without inbreeding effect ranged from 0.968 to 0.995 (P < 0.01). The results indicate loss of productive performance in inbred animals. However, the inclusion of inbreeding coefficient in genetic evaluation models did not alter the magnitude of genetic parameters or genetic trends for the traits studied.


Subject(s)
Inbreeding , Tropical Climate , Pregnancy , Female , Cattle/genetics , Animals , Phenotype , Parturition , Birth Weight
2.
PLoS One ; 18(11): e0286342, 2023.
Article in English | MEDLINE | ID: mdl-37939061

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the function of a cohort of patients with rheumatoid arthritis (RA) from the core set of the International Classification of Functioning and Health (ICF) for RA over 12 months. METHODS: We used prospective longitudinal data to conduct a cohort study among a well-characterized group of RA patients. Ninety RA patients aged between 40 and 70 years were included in the study. Patients were evaluated at baseline and after 12 months. Age, disease duration, current smoking, erosions, disease activity, functional test, disability and physical activity were evaluated. Then, the ICF core set classification for RA was applied. RESULTS: 81 patients completed the assessments, the majority of patients were female (88.9%) and the mean age was 56.5 ± 7.3 years. At baseline, the median disease activity was 3.0. There was a statistically significant (p < 0.02) improvement in "Exercise tolerance functions" over 12 months and also a statistically significant (p < 0.001) decrease in "Muscle strength functions" over 12 months. The activity and participation domain showed a weak correlation with the clinical data of the DAS28-PCR (p<0.02). CONCLUSION: We conclude that relevant aspects of the ICF Core Set for RA were able to adequately express the physical and functional factors of the RA cohort. This tool provides a common language for the interdisciplinary team, which can enhance the use of timely interventions to prevent physical disability in clinical practice.


Subject(s)
Arthritis, Rheumatoid , Disabled Persons , Humans , Male , Female , Adult , Middle Aged , Aged , Cohort Studies , Prospective Studies , Patients , Disability Evaluation
3.
Vet Parasitol ; 322: 110006, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37633244

ABSTRACT

Toxoplasma gondii is an obligate intracellular protozoan of worldwide distribution. It is effective in the infection of various homoeothermic animals of economic importance. The process of T. gondii invasion of host cells occurs in less than 20 s by the active mechanism of penetration. First, a mobile junction is formed due to the association between the apical end of the parasite and the host cell surface. Then, the secretion of invasive and docking proteins allows the formation of the mobile junction before the complete internalization of the parasite. Here, using high-resolution microscopy, it was described new morphological observations of the early events of host cell invasion by tachyzoites of T. gondii. Attempts were made to synchronize the interaction process using low temperatures and treatment of the host cells with cytochalasin D, a drug that interferes with the actin dynamics. Images were obtained showing that the parasite and the host cells seem to release small vesicles with diameters varying from 25 to 100 nm. Furthermore, tunneling nanotubes emerge from the host cell surface and interact with the parasite even at long distance. These observations add new details of adhesion and entry events, such as surface projections of the host cell plasma membrane, pseudopods, and nanotubes radiating from the host cell toward the parasite. In addition, scanning microscopy revealed intense vesiculation, with a morphological characteristic of extracellular microvesicles, during the entry of the tachyzoite into the host cell.


Subject(s)
Toxoplasma , Animals , Toxoplasma/metabolism , Host-Parasite Interactions
4.
J Dent ; 132: 104480, 2023 05.
Article in English | MEDLINE | ID: mdl-36948381

ABSTRACT

OBJECTIVE: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic and to find common risk factors. METHODS: Male patients, older than 50 years, attended their first dental visit to the School of Dentistry for a period of two years, and it was proposed to evaluate undiagnosed type 2 diabetes mellitus. Periodontal, biochemical, microbiological examinations, nutritional profile, and physical activity were performed. RESULTS: A total of 106 patients were examined, 6 (5.6%) had diabetes, and 37 (34.9%) had prediabetes without prior diagnosis. The severity of periodontitis was greater in patients with diabetes. Most of the patients were overweight and had increased systolic blood pressure. Patients with prediabetes and periodontitis had a low adherence to the Mediterranean diet. Tannerella forsythia was present in more patients with periodontitis, and the prevalence of Aggregatibacter actinomycetemcomitans is practically absent in groups with periodontitis, except for the group with diabetes. CONCLUSIONS: In the population studied, the prevalence of patients without a diagnosis of diabetes and prediabetes was very high and underestimated. The increased severity of periodontitis in patients with diabetes and in conjunction with the high level of cortisol seen in patients with periodontitis, especially those with diabetes, emphasize the dysregulation of the immunoinflammatory system. CLINICAL SIGNIFICANCE: It is essential to add all this data to our dental practice to cover patient health with a broader landscape.


Subject(s)
Diabetes Mellitus, Type 2 , Periodontitis , Prediabetic State , Humans , Male , Aged , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Prediabetic State/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Prevalence , Periodontitis/complications , Risk Factors
5.
PLoS One ; 18(1): e0280846, 2023.
Article in English | MEDLINE | ID: mdl-36689423

ABSTRACT

INTRODUCTION: Self-reported disability is potentially influenced by many factors in patients with rheumatoid arthritis (RA). In this sense, we evaluated the association between self-reported disability and (1) clinical features, (2) muscle strength and (3) physical performance over time among patients with RA from two distinct patient cohorts. MATERIALS AND METHODS: Two independent prospective RA cohorts were analyzed. The Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 Joints (DAS28), handgrip test, chair stand test, timed-up-and-go (TUG) test and Short Physical Performance Battery (SPPB) were performed at baseline and in follow-up. T test for independent samples, Mann-Whitney U test, Spearman correlation coefficients and linear regression with generalized estimating equations were performed to assess associations between individual constructs at baseline and over time. RESULTS: A total of 205 total RA patients were included [North American Cohort (n = 115); Brazilian Cohort (n = 90)]. At enrollment, Brazilian men had better HAQ than North American men (p<0.001). Brazilian patients overall had lower muscle strength than North American patients (p<0.05). HAQ was associated with DAS28, handgrip test, chair stand test, TUG and SPPB (p<0.001) in both cohorts. Worsening of the DAS28 and chair stand test were each associated with worsening in HAQ in longitudinal analysis over time. Worsening of handgrip was also associated in with worsening HAQ in both cohorts (p<0.05). A worse TUG test was associated with worsening in HAQ in Brazilian cohort (p<0.05) and a worse SPPB was associated with worsening in HAQ in North American cohort (p<0.05). CONCLUSION: Greater disability measured by HAQ is closely associated with disease activity, pain, muscle strength, and physical performance among RA. Worsening in self-reported disability correlate with worsening clinical factors including objectively-observed physical function.


Subject(s)
Arthritis, Rheumatoid , Hand Strength , Male , Humans , Cohort Studies , Prospective Studies , Disability Evaluation , Surveys and Questionnaires , Severity of Illness Index
7.
Arthritis Res Ther ; 24(1): 171, 2022 07 19.
Article in English | MEDLINE | ID: mdl-35854372

ABSTRACT

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic and systemic inflammation. Besides, it is known that RA patients may present several comorbidities, such as sarcopenia, a condition where patients present both muscle mass and muscle quality impairment. RA treatment is mostly pharmacological and consists in controlling systemic inflammation and disease activity. Despite that, the effect of pharmacological treatment on sarcopenia is not well characterized. OBJECTIVE: To summarize the effects of disease-modifying anti-rheumatic drugs (DMARDs) on skeletal muscle tissue in rheumatoid arthritis (RA) patients. METHODS: A systematic review of randomized clinical trials and observational studies was conducted using MEDLINE, Embase, Cochrane Library, and Web of Science. We selected studies with rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs (DMARDs) that analyzed muscle mass parameters such as lean mass and appendicular lean mass. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Standardized mean difference (SMD) and 95% confidence intervals (CI) were set. A meta-analysis of observational studies was performed using the R software, and we considered significant statistics when p < 0.05. RESULTS: Nine studies were included in this systematic review. In the meta-analysis, DMARD treatment had no positive difference (p = 0.60) in lean mass. In the same way, in the appendicular lean mass parameter, our results showed that DMARDs did not have changes between baseline and post-treatment analysis (p = 0.93). CONCLUSION: There is no evidence of a significant effect of DMARD therapy, either synthetic or biological, on muscle mass. However, this association should be investigated with more studies.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Sarcopenia , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Humans , Inflammation/drug therapy , Muscle, Skeletal , Sarcopenia/chemically induced , Sarcopenia/drug therapy
8.
PLoS One ; 16(11): e0259574, 2021.
Article in English | MEDLINE | ID: mdl-34758045

ABSTRACT

INTRODUCTION: Rheumatoid arthritis(RA) and osteoarthritis(OA) patients showed systemic manifestations that may lead to a reduction in muscle strength, muscle mass and, consequently, to a reduction in functionality. On the other hand, moderate intensity resistance training(MIRT) and high intensity resistance training(HIRT) are able to improve muscle strength and muscle mass in RA and OA without affecting the disease course. However, due to the articular manifestations caused by these diseases, these patients may present intolerance to MIRT or HIRT. Thus, the low intensity resistance training combined with blood flow restriction(LIRTBFR) may be a new training strategy for these populations. OBJECTIVE: To perform a systematic review with meta-analysis to verify the effects of LIRTBFR on muscle strength, muscle mass and functionality in RA and OA patients. MATERIALS AND METHODS: A systematic review with meta-analysis of randomized clinical trials(RCTs), published in English, between 1957-2021, was conducted using MEDLINE(PubMed), Embase and Cochrane Library. The methodological quality was assessed using Physiotherapy Evidence Database scale. The risk of bias was assessed using RoB2.0. Mean difference(MD) or standardized mean difference(SMD) and 95% confidence intervals(CI) were pooled using a random-effects model. A P<0.05 was considered statistically significant. RESULTS: Five RCTs were included. We found no significant differences in the effects between LIRTBFR, MIRT and HIRT on muscle strength, which was assessed by tests of quadriceps strength(SMD = -0.01[-0.57, 0.54], P = 0.96; I² = 58%) and functionality measured by tests with patterns similar to walking(SMD = -0.04[-0.39, 0.31], P = 0.82; I² = 0%). Compared to HIRT, muscle mass gain after LIRTBFR was reported to be similar. When comparing LIRTBFR with low intensity resistance training without blood flow restriction(LIRT), the effect LIRTBFR was reported to be higher on muscle strength, which was evaluated by the knee extension test. CONCLUSION: LIRTBFR appears to be a promising strategy for gains in muscle strength, muscle mass and functionality in a predominant sample of RA and OA women.


Subject(s)
Arthritis, Rheumatoid/physiopathology , Arthritis, Rheumatoid/therapy , Blood Flow Restriction Therapy/methods , Hypertrophy/therapy , Muscle Strength/physiology , Resistance Training , Hemodynamics/physiology , Humans , Hypertrophy/physiopathology
9.
Bioorg Med Chem ; 50: 116467, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34666274

ABSTRACT

Toxoplasma gondiiis an apicomplexan parasite, the causative agent of toxoplasmosis, a common disease in the world. Toxoplasmosis could be severe, especially in immunocompromised patients. The current therapy is limited, where pyrimethamine and sulfadiazine are the best choices despite being associated with side effects and ineffective against the bradyzoites, the parasitic form present during the chronic phase of the infection. Thus, new therapies against both tachyzoites and bradyzoites from T. gondii are urgent. Herein, we present the anti-T. gondii effect of 1,10-phenanthroline and its N-phenyl-1,10-phenanthroline-2-amine derivatives. The chemical modification of 1,10-phenanthroline tonew derivatives improved the anti-T. gondiiactivity 3.4 fold. The most active derivative presented ED50in the nanomolar range, the smallest value found was for Ph8, 0.1 µM for 96 h of treatment. The host cell viability was maintained after the treatment with the compounds, which were found to be highly selective presenting large selectivity indexes. Treatment with derivatives for 96 h was able to eliminate the T. gondii infection irreversibly. The ultrastructural alterations caused after the treatment with the most effective derivative (Ph8) included signs of cell death, specifically revealed by the Tunel assay for detection of DNA fragmentation. The Phen derivatives were also able to control the growth of the in vitro-derived bradyzoite forms of T. gondii EGS strain, causing its lysis and death. These findings promote the 1,10-phenanthroline derivatives as potential lead compounds for the development of a treatment for acute and chronic phases of toxoplasmosis.


Subject(s)
Antiprotozoal Agents/pharmacology , Toxoplasma/drug effects , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Toxoplasma/growth & development
10.
Brain Behav Immun Health ; 11: 100190, 2021 Feb.
Article in English | MEDLINE | ID: mdl-34589727

ABSTRACT

BACKGROUND: Toxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells. METHODS: We evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres. RESULTS: T. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediators. CONCLUSIONS: BrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, these data could be important for future studies aiming at better understanding possible correlations between psychiatric disorders and human CNS infection with T. gondii.

11.
Cells ; 10(9)2021 09 13.
Article in English | MEDLINE | ID: mdl-34572060

ABSTRACT

Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non-communicable diseases, with inflammation being the meeting point among them. Inflammation hitherto includes vascular and tissue changes, but new technologies provide data at the intracellular level that could explain how the cells respond to the aggression more clearly. This review aims to emphasize the molecular pathophysiological mechanisms in patients with type 2 diabetes mellitus and periodontitis, which are marked by different impaired central regulators including mitochondrial dysfunction, impaired immune system and autophagy pathways, oxidative stress, and the crosstalk between adenosine monophosphate-activated protein kinase (AMPK) and the renin-angiotensin system (RAS). All of them are the shared background behind both diseases that could explain its relationship. These should be taken in consideration if we would like to improve the treatment outcomes. Currently, the main treatment strategies in diabetes try to reduce glycemia index as the most important aspect, and in periodontitis try to reduce the presence of oral bacteria. We propose to add to the therapeutic guidelines the handling of all the intracellular disorders to try to obtain better treatment success.


Subject(s)
Diabetes Mellitus/physiopathology , Inflammation/physiopathology , Oxidative Stress , Periodontitis/physiopathology , Animals , Humans
12.
Dalton Trans ; 50(35): 12242-12264, 2021 Sep 14.
Article in English | MEDLINE | ID: mdl-34519725

ABSTRACT

Chagas disease is a neglected tropical disease caused by the protozoan pathogen Trypanosoma cruzi. The disease is a major public health problem affecting about 6 to 7 million people worldwide, mostly in Latin America. The available therapy for this disease is based on two drugs, nifurtimox and benznidazole, which exhibit severe side effects, including resistance, severe cytotoxicity, variable efficacy and inefficiency in the chronic phase. Therefore, new drugs are urgently needed. Coordination compounds may be an interesting alternative for antiparasite therapy against Leishmania spp., Toxoplasma gondii and T. cruzi. Herein, we tested the in vitro effect on T. cruzi epimastigotes (Y strain) of two new µ-oxo Fe(III) dinuclear complexes: [(HL1)(Cl)Fe(µ-O)Fe(Cl)(HL2)](Cl)2·(CH3CH2OH)2·H2O (1) and [(HL2)(Cl)Fe(µ-O)Fe(Cl)(HL2)](Cl)2·H2O (2) where HL1 and HL2 are ligands which contain two pyridines, amine and alcohol moieties with a naphthyl pendant unit yielding a N3O coordination environment. Complexes (1) and (2), which are isomers, were completely characterized, including X-ray diffraction studies for complex (1). Parasites were treated with the complexes and the outcome was analyzed. Complex (1) exhibited the lowest IC50 values, which were 99 ± 3, 97 ± 2 and 110 ± 39 nM, after 48, 72 and 120 h of treatment, respectively. Complex (2) showed IC50 values of 118 ± 5, 122 ± 6 and 104 ± 29 nM for the same treatment times. Low cytotoxicity to the host cell LLC-MK2 was found for both complexes, resulting in impressive selectivity indexes of 106 for complex (1) and 178 for (2), after 120 h of treatment. Treatment with both complexes reduced the mitochondrial membrane potential of the parasite. Ultrastructural analysis of the parasite after treatment with complexes showed that the mitochondria outer membrane presented swelling and abnormal disposition around the kinetoplast; in addition, reservosomes presented anomalous spicules and rupture. The complexes showed low nanomolar IC50 values affecting mitochondria and reservosomes, essential organelles for the survival of the parasite. The low IC50 and the high selectivity index show that both complexes act as a new prototype of drugs against T. cruzi and may be used for further development in drug discovery to treat Chagas disease.


Subject(s)
Coordination Complexes/pharmacology , Drug Development , Ferric Compounds/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Ferric Compounds/chemistry , Humans , Parasitic Sensitivity Tests , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry
13.
Trop Anim Health Prod ; 53(2): 260, 2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33852073

ABSTRACT

This study was realized to analyze the combinations of climatic, physical, and socio-economic variables on distribution of breeding values for performance characteristics and scrotal circumference of Brangus cattle. Records of 84,703 Brangus animals, born from 2000 to 2010 distributed in 65 farms in Brazil were used. The characteristics analyzed were average daily gain from birth to weaning and from weaning to yearling (WW and YW), visual scores of conformations (WC and YC), muscle score (WM and YM), precocity score (WP and YS), and size score (WS and YS) at weaning and yearling and scrotal circumference (SC) at yearling. Components of (co)variance estimated through the animal model employing methodology to AIREML. Mean estimates of direct heritability obtained for visual scores at weaning (WC 0.16, WM 0.16, WP 0.19, and WS 0.22) were lower than those obtained at yearling (YC 0.28, YM 0.26, YP 0.24, and YS 0.40). WW had heritability greater than YW (0.27 and 0.12) and a heritability of 0.36 obtained for SC. Canonical, discriminant, and cluster analyses were performed in the SAS® 9.4 program. Three clusters of genetic values averages per farm were formed according to climatic, physical, and socio-economic variables. Brangus animals are from states of RS, PR, SP, MG, GO, MG, and MS. The highest breeding values were strongly related to thermal amplitude and municipality area. Spatial distribution of the breeding value of Brangus animals can help in the development of environmental indices, genetic evaluations, and the choice of animals for certain environments.


Subject(s)
Economic Factors , Scrotum , Animals , Body Weight , Brazil , Cattle/genetics , Male , Weaning
14.
Int J Sport Nutr Exerc Metab ; 31(1): 21-31, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33248438

ABSTRACT

This study evaluated the effects of inspiratory muscle training (IMT) in glucose control and respiratory muscle function in patients with diabetes. It was a randomized clinical trial conducted at the Physiopathology Laboratory of the Hospital de Clínicas de Porto Alegre. Patients with Type 2 diabetes were randomly assigned to IMT or placebo-IMT (P-IMT), performed at 30% and 2% of maximal inspiratory pressure, respectively, every day for 12 weeks. The main outcome measures were HbA1c, glycemia, and respiratory muscle function. Thirty patients were included: 73.3% women, 59.6 ± 10.7 years old, HbA1c 8.7 ± 0.9% (71.6 ± 9.8 mmol/mol), and glycemia 181.8 ± 57.8 mg/dl (10.5 ± 3.2 mmol/L). At the end of the training, HbA1c was 8.2 ±0.3% (66.1 ± 3.3 mmol/mol) and 8.7 ± 0.3% (71.6 ± 3.3 mmol/mol) for the IMT and P-IMT groups, respectively (p = .8). Fasting glycemia decreased in both groups with no difference after training although it was lower in IMT at 8 weeks: 170.0 ± 11.4 mg/dl(9.4 ± 0.6 mmol/L) and 184.4 ± 15.0 mg/dl (10.2 ± 0.8 mmol/L) for IMT and P-IMT, respectively (p < .05). Respiratory endurance time improved in the IMT group (baseline = 325.9 ± 51.1 s and 305.0 ± 37.8 s; after 12 weeks = 441.1 ± 61.7 s and 250.7 ± 39.0 s for the IMT and P-IMT groups, respectively; p < .05). Considering that glucose control did not improve, IMT should not be used as an alternative to other types of exercise in diabetes. Higher exercise intensities or longer training periods might produce better results. The clinical trials identifier is NCT03191435.


Subject(s)
Blood Glucose/metabolism , Breathing Exercises , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , Muscle Strength , Respiratory Muscles/physiology , Adult , Aged , Albuminuria , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/urine , Female , Glycated Hemoglobin/analysis , Humans , Intention to Treat Analysis , Lung/physiology , Male , Middle Aged , Spirometry
15.
Article in English | MEDLINE | ID: mdl-32714877

ABSTRACT

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite. Toxoplasma can invade and multiply inside any nucleated cell of a wide range of homeothermic hosts. The canonical process of internalization involves several steps: an initial recognition of the host cell surface and a sequential secretion of proteins from micronemes followed by rhoptries that assemble a macromolecular complex constituting a specialized and transient moving junction. The parasite is then internalized via an endocytic process with the establishment of a parasitophorous vacuole (PV), that does not fuse with lysosomes, where the parasites survive and multiply. This process of host cell invasion is usually referred to active penetration. Using different cell types and inhibitors of distinct endocytic pathways, we show that treatment of host cells with compounds that interfere with clathrin-mediated endocytosis (hypertonic sucrose medium, chlorpromazine hydrochloride, and pitstop 2 inhibited the internalization of tachyzoites). In addition, treatments that interfere with macropinocytosis, such as incubation with amiloride or IPA-3, increased parasite attachment to the host cell surface but significantly blocked parasite internalization. Immunofluorescence microscopy showed that markers of macropinocytosis, such as the Rab5 effector rabankyrin 5 and Pak1, are associated with parasite-containing cytoplasmic vacuoles. These results indicate that entrance of T. gondii into mammalian cells can take place both by the well-characterized interaction of parasite and host cell endocytic machinery and other processes, such as the clathrin-mediated endocytosis, and macropinocytosis.


Subject(s)
Toxoplasma , Toxoplasmosis , Animals , Endocytosis , Host-Parasite Interactions , Pinocytosis , Vacuoles
16.
Head Neck Pathol ; 14(3): 598-605, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31552621

ABSTRACT

Evaluation and comparison of odontogenic keratocysts and detigerous cysts immunoexpression and immunostaining intensities of Ki-67 antigen by assessing the whole extent of the epithelium (all epithelium layers in combination) and each layer individually. Ki-67 immunoexpression was evaluated in 15 odontogenic keratocysts and 6 dentigerous cysts using automated methods and the Aperio Technologies Inc. computer system. No statistically significant differences were observed in immunoexpression nor in immunostaining intensities between both lesions. Also, no statistically significant differences were found between odontogenic keratocysts from maxilla versus mandible nor primary versus recurrent. However, odontogenic keratocyst showed a significantly higher cellular proliferation index in the suprabasal layers compared to the basal layer. Assessment of the cellular proliferation index through a computerized system enabled the evaluation of all epithelial tissue without field selection. The increased Ki-67 immunoexpression in suprabasal layers of odontogenic keratocyst suggests a different biological behavior and more aggressive proliferation potential when compared to dentigerous cyst. The same result was found in recurrent odontogenic keratocysts when compared with primary ones. The odontogenic keratocysts of the maxilla and mandible have similar Ki-67 immunoexpression. The evaluation of cellular proliferation only by immunohistochemical analysis with Ki-67 antigen does not provide enough data to elucidate the biological behavior of odontogenic keratocyst.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Ki-67 Antigen/analysis , Odontogenic Cysts/pathology , Cell Proliferation , Humans
17.
Rev. bras. odontol ; 76(1): 1-6, jan. 2019. ilust, tab
Article in English | LILACS | ID: biblio-1121848

ABSTRACT

Objetivo: analisar artigos científicos sobre o índice de proliferação celular usando o anticorpo anti-Ki-67 em ceratocistos odontogênicos e comparar esses trabalhos para estimar um índice médio para essa lesão. Material e Métodos: dois pesquisadores realizaram a busca literária de forma independente na base de dados MEDLINE/PubMed e 28 artigos contendo dados relevantes foram selecionados. Resultados: a análise imuno-histoquímica utilizada nos artigos avaliados mostrou-se muito variável, não apresentando metodologias claras e unificadas, tornando a comparação entre os diferentes resultados difícil. Conclusão: Considerando o ceratocisto odontogênico uma lesão de comportamento clínico incomum, uma classificação adequada é necessária, assim como um tratamento apropriado com um bom prognostico deve ser estabelecido para o paciente de acordo com sua natureza. Dessa forma, um protocolo de análise imuno-histoquímica deve ser estabelecido para que possamos obter dados confiáveis sobre essa lesão


Objective: this review aims to analyze scientific articles about cell proliferation index using Ki-67 in odontogenic keratocyst and compare these papers to estimate the average index of this lesion. Material and Methods: two researchers performed a literature search independently in the MEDLINE/PubMed database and 28 articles containing relevant data were selected. Results: the immunohistochemical analysis methodology showed great variability among all the papers, with unclear and unified methodologies, making the comparison among different studies difficult. Conclusion: considering odontogenic keratocyst as a lesion with an uncommon clinical behavior, an adequate classification for it is necessary, so an appropriate treatment with a good prognosis for the patient can be established according to its nature. A standardization is needed so immunohistochemical analyses will find reliable data to classify properly this lesion


Subject(s)
Pathology, Oral , Odontogenic Cysts , Odontogenic Tumors , Cell Proliferation , Antigens
18.
Parasitol Res ; 117(9): 2795-2805, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29934691

ABSTRACT

We have previously shown that metallocomplexes can control the growth of Toxoplasma gondii, the agent that causes toxoplasmosis. In order to develop new metallodrugs to treat this disease, we investigated the influence of the coordination of sulfadiazine (SDZ), a drug used to treat toxoplasmosis, on the biological activity of the iron(III) complex [Fe(HBPClNOL)Cl2]·H2O, 1, (H2BPClNOL=N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)(3-chloro)(2-hydroxy)-propylamine). The new complex [(Cl)(SDZ)Fe(III)(µ-BPClNOL)2Fe(III)(SDZ)(Cl)]·2H2O, 2, which was obtained by the reaction between complex 1 and SDZ, was characterized using a range of physico-chemical techniques. The cytotoxic effect of the complexes and the ability of T. gondii to infect LLC-MK2 cells were assessed. It was found that both complexes reduced the growth of T. gondii while also causing low cytotoxicity in the host cells. After 48 h of treatment, complex 2 reduced the parasite's ability to proliferate by about 50% with an IC50 of 1.66 µmol/L. Meanwhile, complex 1 or SDZ alone caused a 40% reduction in proliferation, and SDZ displayed an IC50 of 5.3 µmol/L. In addition, complex 2 treatment induced distinct morphological and ultrastructural changes in the parasites and triggered the formation of cyst-like forms. These results show that the coordination of SDZ to the iron(III) complex is a good strategy for increasing the anti-toxoplasma activity of these compounds.


Subject(s)
Cell Proliferation/drug effects , Iron/pharmacology , Sulfadiazine/pharmacology , Toxoplasma/growth & development , Toxoplasmosis/drug therapy , Animals , Cell Line , Cell Survival/drug effects , Macaca mulatta , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Toxoplasma/drug effects , Toxoplasmosis/parasitology
19.
Parasitol Int ; 64(6): 622-31, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26335616

ABSTRACT

Toxoplasmosis is a widely disseminated disease caused by Toxoplasma gondii, an intracellular protozoan parasite. Standard treatment causes many side effects, such as depletion of bone marrow cells, skin rashes and gastrointestinal implications. Therefore, it is necessary to find chemotherapeutic alternatives for the treatment of this disease. It was shown that a naphthoquinone derivative compound is active against T. gondii, RH strain, with an IC50 around 2.5 µM. Here, three different naphthoquinone derivative compounds with activity against leukemia cells and breast carcinoma cell were tested against T. gondii (RH strain) infected LLC-MK2 cell line. All the compounds were able to inhibit parasite growth in vitro, but one of them showed an IC50 activity below 1 µM after 48 h of treatment. The compounds showed low toxicity to the host cell. In addition, these compounds were able to induce tachyzoite-bradyzoite conversion confirmed by morphological changes, Dolichus biflorus lectin cyst wall labeling and characterization of amylopectin granules in the parasites by electron microscopy analysis using the Thierry technique. Furthermore, the compounds induced alterations on the ultrastructure of the parasite. Taken together, our results point to the naphthoquinone derivative (LQB 151) as a potential compound for the development of new drugs for the treatment of toxoplasmosis.


Subject(s)
Antiprotozoal Agents/pharmacology , Naphthoquinones/pharmacology , Toxoplasma/drug effects , Toxoplasma/growth & development , Toxoplasmosis, Animal/drug therapy , Animals , Cell Line , Cell Survival/drug effects , Macaca mulatta , Microscopy, Electron , Structure-Activity Relationship , Toxoplasmosis, Animal/parasitology
20.
Ciênc. rural ; 44(12): 2258-2264, 12/2014. tab
Article in Portuguese | LILACS | ID: lil-729814

ABSTRACT

Objetivou-se estimar as correlações fenotípicas (r) entre os escores comportamentais de reatividade aplicados durante e após a pesagem e os ganhos médios diários de peso (GMD) de cordeiros cruzados Suffolk x Île-de-France, aos 30, 60 e 90 dias de idade, bem como estudar o efeito da habituação dos animais ao manejo. As variáveis avaliadas por meio de escores foram: interferência do avaliador para o animal entrar na balança (INT), vocalização (VOC), movimentação (MOV), tensão (TEN), movimentos exploratórios (ME), postura de orelhas (ORE) e o teste de tipos de marcha (TM). Os resultados das correlações de Spearman obtidos entre os escores indicam que VOC, MOV e TEN podem ser consideradas como características importantes na expressão da reatividade de ovinos em ambiente de restrição. Já o GMD parece não estar associado com a reatividade dos cordeiros avaliados. Por fim, aos 90 dias de idade, os cordeiros apresentaram-se menos reativos, em função do aprendizado por habituação.


The aim of this study was to estimate the phenotypic correlations (r) between behavioral reactivity scores obtained during and after weighing, and the average daily weight gains (ADG) of Suffolk x Île-de-France cross lambs, at 30, 60 and 90 days of age, as well as to study the effect of habituation towards handling. The variables assessed through scores were: interference of the observer for the animal to enter the weighing crate (INT), vocalization (VOC), movement (MOV), tension (TEN), exploratory movements (EM), ears posture (EP) and the gait speed test (qualitative flight time test) (GS). The results of the Spearman correlations indicate that VOC, MOV and TEN may be considered important traits in the expression of reactivity in sheep assessed while restrained. On the contrary, ADG does not seem to be correlated with reactivity. Finally, at 90 days of age, the lambs were less reactive, due to learning by habituation.

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