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1.
Toxicon ; 242: 107692, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38513828

RESUMO

The aim was to report cases and risk factors for hepatogenous photosensitization in lambs kept on Brachiaria spp. pastures and supplemented with levels of extruded urea (EU). The herd consisted of 69 Texel crossbred lambs with known parentage (fathers and mothers adapted to the consumption of forage of the genus Brachiaria), randomly divided into 5 groups and distributed in individual paddocks for each group. The animals were supplemented with increasing levels of EU (Amireia® 200S): 0, 6, 12, 18, and 24 g of EU per 100 kg-1 of body weight (BW). The concentration of protodioscin was estimated in the mixed pastures of Brachiaria spp. (cv. Marandu and cv. Basilisk), structural components (leaf, stem, and dead material), samples of each cultivar, and in the months of December (2018), February, and April (2019). The animals were examined daily, and when behavioral changes were identified, they underwent clinical examinations and anamnesis. Weighing was performed every 14 days, followed by necropsy and serum biochemical analysis, including gamma-glutamyltransferase (GGT). The highest concentrations of protodioscin (p < 0.0001) were found in the pastures used by animals supplemented without extruded urea (7.07 ± 0.56), in the Basilisk cultivar (11.35 ± 0.06), in the leaf blade components (2.08 ± 0.05), and thatch (2.20 ± 0.00), and in the month of April (7.34 ± 0.29) (the month with the lowest rainfall), respectively. Fourteen (20.29%) cases of photosensitization were observed in lambs, of which six recovered, and eight died. Serum GGT levels ranged from 42.2 to 225 IU/L; however, in animals that died, values ranged from 209.4 to 225 IU/L. The use of levels 12 g and 18 g per 100 kg-1 of body weight of extruded urea may contribute to the lower occurrence of photosensitization, as the animals selected pastures with lower protodioscin content, presenting a smaller number of cases.


Assuntos
Brachiaria , Diosgenina , Ureia , Animais , Masculino , Ração Animal/análise , Brasil , Suplementos Nutricionais , Diosgenina/análogos & derivados , gama-Glutamiltransferase/sangue , Transtornos de Fotossensibilidade/veterinária , Saponinas , Ovinos , Doenças dos Ovinos , Ureia/sangue , Feminino
2.
Clin Exp Gastroenterol ; 16: 213-224, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023814

RESUMO

Purpose: Inflammatory bowel disease (IBD) is a disease of increasing prevalence in developing countries. Obesity has emerged as a potential risk for IBD; however, the data in the literature are conflicting, and relevant studies in Brazil are limited. Here, we report body mass index profile (BMI) of patients with IBD treated at reference centers in three states of northeastern Brazil. Patients and Methods: Observational descriptive study conducted from January 2021 through December 2021 in patient with IBD. Results: Of 470 patients with IBD, 194 (41%) were classified as normal weight, 42 (9%) as underweight, 155 (33%) as overweight, and 79 (17%) as obese; CD patients were significantly more likely to be underweight than UC patients (p=0.031)Overweight patients were older (median age: 47 years) than normal-weight and underweight patients at diagnosis (38.5 and 35.5 years, respectively [p<0.0001]). IBD onset and diagnosis among overweight and obese individuals were associated with older age. More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD, irrespective of nutritional status. There was a higher frequency of compatible symptoms with axial joint inflammation among obese patients (p=0.005) and a lower frequency of compatible symptoms with peripheral joint inflammation in underweight patients (p=0.044) than in patients of normal weight. No significant difference in the frequency of different drug or surgical treatments was observed among the groups. Conclusion: Despite the predominance of overweight and obesity in patients with IBD, no differences in the patterns of disease were seen between the overweight and normal-weight groups; however, obesity was associated with IBD onset in older adults and a higher frequency compatible symptom with axial joint inflammation. These data reinforce the importance of monitoring the nutritional status of IBD patients and the need for a multidisciplinary approach, as recommended in the current guidelines.

3.
Commun Biol ; 6(1): 1058, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853179

RESUMO

Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/metabolismo , Catepsinas , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Inibidores de Proteases/farmacologia , Cisteína Endopeptidases/metabolismo
4.
J Eval Clin Pract ; 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37840239

RESUMO

RATIONALE: In the context of a major health crisis, health professionals must first compare patients' recovery prospects, thus giving priority to the goal of saving the greatest number of lives. AIMS AND OBJECTIVES: Critically evaluate a protocol for allocation of scarce intensive care units (ICU), which the authors proposed at the onset of the COVID-19 pandemic and originally published in two Brazilian newspapers; and compare that protocol with similar proposals, particularly with 2 successive protocols issued by the Brazilian Critical Care Association. The main objective is to highlight the advantages of the authors' approach and discuss some criticisms that has been levelled against the proposed protocol after its original publication in 2020. METHOD: Comparative analysis of 3 different protocols (the authors' proposed protocol and 2 successive protocols issued by the Brazilian Critical Care Association) with regard to ethical principles. RESULTS: The main objective of a healthcare system is to ensure a fair patient triage process when it is impossible to grant admission to all patients in need of treatment. Decision-making regarding the impartial prioritization of ICU admissions must be based primarily on clinical criteria. The Sequential Organ Failure Assessment (SOFA) is, for ethical and technical reasons, a useful tool for clinical assessments of patients. Based on three ranges of SOFA scores, patients can be classified into a "high", a "medium", and a "low" priority group. In the case of ties, the life cycle principle must be the tiebreaker. If the tie persists, a draw must be used. CONCLUSION: The authors' proposed protocol has advantages over the other two protocols due to its greater practicality and capacity to account for egalitarian and consequentialist principles simultaneously. It aims at saving as many lives as possible within the constraints of fairness. Furthermore, the proposed protocol avoids discrimination against people with disabilities without, at the same time, promoting discrimination against the elderly.

5.
Clin Exp Gastroenterol ; 16: 87-99, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37366396

RESUMO

Purpose: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBDs) with multifactorial causes. They are becoming more prevalent in developing countries such as Brazil; however, relevant studies in poorer regions of the country are limited. Here, we report the clinical-epidemiological profile of patients with IBD treated at reference centers in three states of Northeast Brazil. Patients and Methods: This was a prospective cohort study involving patients at referral outpatient clinics for IBD from January 2020 through December 2021. Results: Of 571 patients with IBD, 355 (62%) had UC, and 216 (38%) had CD. The patients were predominantly women (355, 62%) for both UC and CD. Extensive colitis was the pattern present in 39% of the UC cases. For CD, ileocolonic disease was the predominant manifestation (38%), with 67% of cases showing penetrating and/or stenosing behavior. The majority of patients were diagnosed between the ages of 17 and 40, corresponding to 60.2% in CD and 52.7% in UC. The median time between symptom onset and diagnosis was 12 months for CD and 8 months for UC (p=0.042). Joint involvement was the most frequent extraintestinal manifestation, with arthralgia and arthritis present in 41.9% and 18.6% of the patients, respectively. Biological therapy was prescribed to 73% of CD patients and 26% of UC patients. A progressive increase in new cases was observed in every 5-year interval over the last five decades, with 58.6% being diagnosed in the last 10 years. Conclusion: More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD. A prolonged time to diagnosis may have contributed to these findings. A progressive increase in IBD incidence was observed and may be related to greater urbanization and better access to specialized outpatient clinics, resulting in improvements in diagnosis.

6.
J Neurochem ; 163(2): 113-132, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35880385

RESUMO

COVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment.


Assuntos
COVID-19 , Animais , Astrócitos , Carbono , Cricetinae , Modelos Animais de Doenças , Glucose , Glutamina , Ácidos Cetoglutáricos , Mesocricetus , Piruvatos , SARS-CoV-2
7.
ISA Trans ; 128(Pt A): 581-592, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34815072

RESUMO

A robust current control approach with disturbance cross-coupling compensation for permanent magnet synchronous motor drives (PMSM) is proposed in this paper. The proposed approach can enhance the reference tracking and provides a robust option for current control of PMSM drives. A discrete-time sliding mode current controller is proposed. The PMSM model includes the digital implementation delay, present due to the discrete-time algorithm execution. A discrete-time backstepping disturbance observer is developed, being combined to the sliding mode controller as a means to improve the robustness and tracking capability. The effects of coupling, parametric uncertainties and load disturbances are compensated by the backstepping disturbance observer. The stability analysis of the combined system is presented and the limits for overall system stability are discussed. Simulations and experimental results validate the combined scheme and demonstrate the good performance of the proposal.

8.
Toxicon ; 203: 115-116, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34662630

RESUMO

The aim of the present study was to describe an outbreak of poisoning by abamectin in calves less than four months of age whose mothers were treated with a pour-on product containing this ingredient. The diagnosis was based on the history, clinical signs, absence of macroscopic and histopathological findings (characteristic of this type of poisoning) and the detection of abamectin in tissues of the animals submitted to necropsy. Based on this report, the recommendation is the use with caution of pour-on formulations containing abamectin on cows having given birth less than four months earlier.


Assuntos
Anti-Helmínticos , Doenças dos Bovinos , Animais , Bovinos , Doenças dos Bovinos/induzido quimicamente , Doenças dos Bovinos/tratamento farmacológico , Feminino , Ivermectina/análogos & derivados , Ivermectina/toxicidade
9.
J Fungi (Basel) ; 6(3)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887256

RESUMO

Paracoccidioidomycosis (PCM) is a granulomatous fungal disease caused by the dimorphic fungal species of Paracoccidioides, which mainly affects the lungs. Modern strategies for the treatment and/or prevention of PCM are based on a Th1-type immune response, which is important for controlling the disease. One of the most studied candidates for a vaccine is the P10 peptide, derived from the 43 kDa glycoprotein of Paracoccidioides brasiliensis. In order to improve its immune modulatory effect, the P10 peptide was associated with a chitosan-conjugated nanoparticle. The nanoparticles presented 220 nm medium size, poly dispersion index (PDI) below 0.5, zeta potential of +20 mV and encapsulation efficiency around 90%. The nanoparticles' non-toxicity was verified by hemolytic test and cell viability using murine macrophages. The nanoparticles were stable and presented physicochemical characteristics desirable for biological applications, reducing the fungal load and the usual standard concentration of the peptide from 4 to 20 times.

10.
J Surg Oncol ; 121(5): 743-758, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31970785

RESUMO

INTRODUCTION: Soft tissue sarcomas (STSs) are rare tumors and constitute only 1% of all tumors in adults. Indeed, due to their rarity, most cases in Brazil are not treated according to primary international guidelines. METHODS: This consensus addresses the treatment of STSs in the extremities. It was made by workgroups from Brazilian Societies of Surgical Oncology, Orthopaedics, Clinical Oncology, Pathology, Radiology and Diagnostic Imaging, and Radiation Oncology. The workgroups based their arguments on the best level of evidence in the literature and recommendations were made according to diagnosis, staging, and treatment of STSs. A meeting was held with all the invited experts and the topics were presented individually with the definition of the degree of recommendation, based on the levels of evidence in the literature. RESULTS: Risk factors and epidemiology were described as well as the pathological aspects and imaging. All recommendations are described with the degree of recommendation and levels of evidence. CONCLUSION: Recommendations based on the best literature regional aspects were made to guide professionals who treat STS. Separate consensus on specific treatments for retroperitoneal, visceral, trunk, head and neck sarcomas, and gastrointestinal stromal tumor, are not contemplated into this consensus.


Assuntos
Extremidades/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Biópsia , Brasil , Quimioterapia Adjuvante , Extremidades/cirurgia , Humanos , Linfonodos/patologia , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/terapia , Estadiamento de Neoplasias , Cuidados Paliativos , Complicações Pós-Operatórias/terapia , Radioterapia Adjuvante , Fatores de Risco , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia
11.
Acta Trop ; 201: 105213, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31600523

RESUMO

The aim of the present study was to evaluate the in vitro effect of quercetin combined with ivermectin (IVM) on Haemonchus contortus larvae and adults with different resistance profiles and demonstrate the in vivo anthelmintic action of this combination when used in sheep naturally infected. The effect of combination was evaluated based on the analysis of the mean effective concentration (EC50) obtained for larvae using the larval migration inhibition test and for adults using the motility test on females. The tests with larvae and adults were conducted using isolates with different degrees of susceptibility to IVM (sensitive, intermediate and highly resistant). The in vivo effect was evaluated based on the reduction in the egg count (FEC) and reduction in the count of adult helminths recovered after parasitological necropsy. Using the combination of quercetin with IVM, it was observed that in larvae, quercetin did not significantly reduce the EC50 for IVM in the sensitive and highly resistant isolates, but led to a significant reduction in the EC50 for IVM in the intermediate isolate. In adults, quercetin did not significantly reduce the EC50 for IVM in any of the isolates. No significant effect of the combination was found regarding the reduction in FEC or total count of parasites. The results of the in vitro and in vivo tests performed in the present study on quercetin activity underscore the importance of evaluating resistance-reversing agents among different stages of parasite development as well as among isolates with different resistance profiles. The action of quercetin combined with IVM on the motility of H. contortus larvae and adults was influenced by the degree of resistance and development stage of the parasite. The combination was effective only on intermediate resistant larvae. No action of the combination against adults was found. Moreover, this combination, when administered through the intra-abomasal route, was not effective at reducing the FEC and parasite load of naturally infected sheep.


Assuntos
Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Hemoncose/tratamento farmacológico , Haemonchus/efeitos dos fármacos , Ivermectina/uso terapêutico , Larva/efeitos dos fármacos , Quercetina/uso terapêutico , Doenças dos Ovinos/tratamento farmacológico , Animais , Feminino , Masculino , Contagem de Ovos de Parasitas , Ovinos/parasitologia , Doenças dos Ovinos/parasitologia
12.
Rev. colomb. psiquiatr ; 47(3): 140-147, jul.-set. 2018. tab, graf
Artigo em Inglês | LILACS, COLNAL | ID: biblio-978314

RESUMO

ABSTRACT Objective: In Latin America is not known for certain the quantity or quality of therapeutic communities (TCs) available in the region. The objective of this study is to describe and quantify the quantity and quality of the existing TCs in 5 different countries. Design: A multicenter quantitative description of the TCs was conducted in Argentina, Brazil, Colombia, Mexico and Peru. Methods: A survey was realized through the TCs regulatory entities of each country that accepted to participate in the study. Results: Of the 285 TCs identified in the 5 countries, 176 (62%) accepted to participate in this study. The TCs quality vas evaluated according to the scoring system stablished by De Leon, finding that 70% of the facilities have scores of 11/12 or 12/12 using these criteria. We also found that the majority of the De Leon criteria are known by more than 90% of the institutions, however, the dimensions of "separation of the community" and "encounter groups between residents" were the least known with 63 and 85% respectively. The main reasons for abandonment of TCs were "not accepting the rules of the institution", "lack of money" and "not feeling comfortable with the facilities". 98% of the TCs provided services to other substance abuse problems, 94% for alcohol and 40% for other types of substances. Conclusions: The majority of the TCs identified in our sample meet the quality criteria stablished by De Leon, mostly providing services for substance abuse. However, they should put in place additional policies to improve the unfulfilled conditions and investigate the reasons for the dissatisfaction and abandonment of these institutions.


RESUMEN Objetivo: En Latinoamérica no se conoce a ciencia cierta la cantidad o la calidad de las comunidades terapéuticas disponibles en los distintos países de la región. El objetivo de este estudio es identificar y describir la cantidad y la calidad de las comunidades terapéuticas existentes en 5 países de la región. Diseño: Se realizó un estudio multicéntrico descriptivo cuantitativo de las comunidades terapéuticas en Argentina, Brasil, Colombia, México y Perú. Métodos: Mediante las entidades reguladoras de las comunidades terapéuticas de cada país, se realizó una encuesta a las que aceptaran participar en el estudio. Resultados: De las 285 comunidades terapéuticas identificadas en los 5 países, 176 (62%) aceptaron participar en el estudio. La calidad de las comunidades terapéuticas se evaluó por las puntuaciones establecidas con los criterios de De León; se encontró que el 70% de las instituciones tienen puntuaciones de 11/12 o 12/12 según estos criterios. También se encontró que cumplen la mayoría de los criterios de De León más del 90% de las instituciones; sin embargo, las dimensiones «separación de la comunidad¼ y «grupos de encuentro entre residentes¼ fueron los menos cumplidos (el 63 y el 85% de las comunidades respectivamente). Las principales razones de abandono de las comunidades terapéuticas fueron no aceptar las normas de la institución, falta de recursos económicos y no sentirse a gusto con ella. El 98% de las comunidades terapéuticas prestaban servicios para problemas de abuso de otras sustancias, el 94% para abuso de alcohol y el 40% para otros tipos de abusos. Conclusiones: La mayoría de las comunidades terapéuticas identificadas en nuestra muestra cumplen los criterios de calidad establecidos por De León, y en su gran mayoría prestan servicios para abuso de sustancias, pero deben instaurarse políticas para mejorar las condiciones no cumplidas e indagar los motivos de las disconformidades y el abandono de estas instituciones.


Assuntos
Humanos , Masculino , Feminino , Grupos de Treinamento de Sensibilização , Comunidade Terapêutica , Ciência , Características de Residência , Inquéritos e Questionários , Transtornos Relacionados ao Uso de Substâncias , Gestão da Qualidade Total , Alcoolismo , Emoções , América Latina , Métodos
13.
Nat Prod Res ; 32(22): 2720-2723, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28927283

RESUMO

Secondary metabolites isolated from Simira eleiezeriana and Simira glaziovii were evaluated against herpes simplex virus (HSV-1) and (HSV-2). The 50% effective concentrations values (EC50) were calculated from the dose-response curve and the selectivity index (SI) against the virus. The physicochemical data LogP, (PSA), (NRB), (HBA) and (HBD) were obtained using Marvin Sketch. Among the tested compounds, conipheraldeyde, harman and simirane A showed better results with EC50 6.39; 4.90; 4.61 µg/mL and SI 78.3; 11.8; 7.01, respectively, for HSV-1, and EC50 41.2; 71.8; 3.73 µg/mL and SI 12.1; 24.7; 8.7, respectively, for HSV-2. The percentage of inhibition (PI) obtained for HSV-1 were higher than 60%, and for HSV-2 these compounds showed PI > 90%. The physical chemical data showed that the most active compounds satisfy the attributes for drugs with good oral bioavailability.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Rubiaceae/química , Animais , Antivirais/isolamento & purificação , Chlorocebus aethiops , Compostos Fitoquímicos/isolamento & purificação , Casca de Planta/química , Células Vero
14.
Subst Abuse Treat Prev Policy ; 12(1): 53, 2017 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-29262838

RESUMO

BACKGROUND: In Latin America, substance related disorders are highly prevalent and one of the treatment strategies is the Therapeutic Communities (TCs), however, in Latin America there is scarce data about this treatment strategies, their quality, drop-out rates and patient satisfaction. METHODS: Based on a previous study in 5 Latin American countries, the TCs who had a score equal or higher than 9 according to the De Leon criteria which are some fundamental items that the TCs should meet, were selected to carry out a descriptive and retrospective study of qualitative and quantitative characteristics of the TCs. RESULTS: Data from 58 TCs in 5 countries were included, with a sample of 1414 patients interviewed, of which most were single men, with no hospitalization history in a therapeutic community. Marijuana was the most commonly substance used in the 30 days prior to hospitalization, with 78% of interviewees referring alcohol consumption in the last 6 months and an average onset of psychoactive substances at 16 years of age. A 79% of the patients interviewed perceived some improvement during their stay in the TCs. The less fulfilled Quality Indicators by the TCs were "Requesting a professional qualification to former addicts that belonged to the program" and "Work as part of the therapeutic program". Among the reasons for discharge found in the database, 44% were due to therapeutic discharge with fulfillment of the treatment plan and 44% withdraws. CONCLUSION: The user satisfaction with TCs, in terms of infrastructure and quality are quite high, as the fulfillment of essential quality items, however, the follow up information to evaluate effectiveness of the treatment is poor or in some cases unknown.


Assuntos
Internacionalidade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Comunidade Terapêutica , Feminino , Humanos , América Latina , Masculino , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários
15.
PLoS Negl Trop Dis ; 11(7): e0005725, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28704363

RESUMO

BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. CONCLUSION: Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.


Assuntos
Clofazimina/administração & dosagem , Dapsona/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase Multibacilar/tratamento farmacológico , Rifampina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Quimioterapia Combinada/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Immunobiology ; 220(8): 1006-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25956455

RESUMO

OBJECTIVES: To evaluate the expression of Galectins (Gal) 1, 3 and 9, Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients with potentially malignant disorders (PMD) and oral squamous cell carcinomas (OSCC) by comparison with the controls. STUDY DESIGN: We selected 40 cases of PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry was performed for Gal-1, Gal-3, Gal-9 and MMP-3. RESULTS: Gal-9 was significantly higher in patients with OSCC than in others groups (p < 0.001). Gal-1 expression was significantly lower in patients with leukoplakia than those with OSCC and controls (p = 0.0001). Gal-3 was significantly lower in patients with OSCC than those with leukoplakia (p = 0.03). MMP-3 was lower in patients with leukoplakia in comparison with the lichen planus group (p = 0.013). CONCLUSION: The increased expression of Gal-9 may be helpful to differentiate of OSCC from other oral cavity lesions.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Galectinas/metabolismo , Leucoplasia/diagnóstico , Líquen Plano/diagnóstico , Mastócitos/imunologia , Metaloproteinase 3 da Matriz/metabolismo , Neoplasias Bucais/diagnóstico , Benzamidas/metabolismo , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Galectina 3/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Bucais/patologia , Tirosina/análogos & derivados , Tirosina/metabolismo
17.
Immunobiology ; 220(1): 154-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25204704

RESUMO

BACKGROUND: Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into understanding the natural course of the disease and its clinical manifestations, hence contributing to the development of preventive measures and treatment proposals. The aim of this study was to evaluate the histopathological and immunological aspects involved in the role of different effector and regulatory responses, as well as the correlation between the TLRs, Galectins, Matrix Metalloproteinases and cytoplasmic proteases of mast cells in this infection. METHODS: Sixteen biopsy specimens with oral lesions of chronic PCM, as well as 13 sections of normal oral mucosa were analyzed. Histopathological and immunological aspects involved in the role of different effector and regulatory responses were evaluated. Indirect immunohistochemistry was performed for IL-17, IL-10, IL-4, TGF-ß, FoxP3, Gal-1, Gal-3, Gal-9, TLR-2, TLR-4, MMP-3 and MMP-9, as well as for chymase and tryptase for mast cells identification. Fibrosis was quantified using Picrosirius. RESULTS: There was a significant increase in the area of fibrosis and in the number of cells expressing IL-10, IL-4, IL-17, FoxP3, Gal-3, TLR-2, MMP3 and MMP9 in patients with PCM in comparison with patients in the group control. There was no difference in the expression of TGF-ß, TLR-4, Gal-1 or Gal-9. Mast cells number was found to be significantly lower in oral chronic PCM when compared to control samples after quantification of mast cells and expression of chymase and tryptase. PCM granulomas were classified to the morphological aspects in organized ou non-organized. Expression of IL-4 in non-organized granulomas was significantly higher. CONCLUSION: The proteins studied herein appear to play an important role in the development and maintenance of oral lesions of PCM, as well as in the processes of development and progression of lesions caused by the fungus and by the immune response associated with the infection.


Assuntos
Citocinas/metabolismo , Galectinas/metabolismo , Metaloproteinases da Matriz/metabolismo , Doenças da Boca , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/metabolismo , Receptores Toll-Like/metabolismo , Biópsia , Contagem de Células , Humanos , Imuno-Histoquímica , Mastócitos/imunologia , Mastócitos/metabolismo , Paracoccidioidomicose/patologia
18.
PLoS One ; 9(10): e107747, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25314118

RESUMO

Rio de Janeiro is endemic for tuberculosis (TB) and presents the second largest prevalence of the disease in Brazil. Here, we present the bacterial population structure of 218 isolates of Mycobacterium tuberculosis, derived from 186 patients that were diagnosed between January 2008 and December 2009. Genotypes were generated by means of spoligotyping, 24 MIRU-VNTR typing and presence of fbpC103, RDRio and RD174. The results confirmed earlier data that predominant genotypes in Rio de Janeiro are those of the Euro American Lineages (99%). However, we observed differences between the classification by spoligotyping when comparing to that of 24 MIRU-VNTR typing, being respectively 43.6% vs. 62.4% of LAM, 34.9% vs. 9.6% of T and 18.3% vs. 21.5% of Haarlem. Among isolates classified as LAM by MIRU typing, 28.0% did not present the characteristic spoligotype profile with absence of spacers 21 to 24 and 32 to 36 and we designated these conveniently as "LAM-like", 79.3% of these presenting the LAM-specific SNP fbpC103. The frequency of RDRio and RD174 in the LAM strains, as defined both by spoligotyping and 24 MIRU-VNTR loci, were respectively 11% and 15.4%, demonstrating that RD174 is not always a marker for LAM/RDRio strains. We conclude that, although spoligotyping alone is a tool for classification of strains of the Euro-American lineage, when combined with MIRU-VNTRs, SNPs and RD typing, it leads to a much better understanding of the bacterial population structure and phylogenetic relationships among strains of M. tuberculosis in regions with high incidence of TB.


Assuntos
Repetições Minissatélites/genética , Mycobacterium tuberculosis/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/microbiologia , Alelos , Proteínas de Bactérias/genética , Brasil , Frequência do Gene , Genótipo , Humanos , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia
19.
J Endod ; 40(2): 199-203, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24461404

RESUMO

INTRODUCTION: Cysts and periapical granulomas are inflammatory reactions that develop in response to periapical infection by microbial species in dental root canal. It is known that toll-like receptors (TLRs) are pathogen recognition molecules and that galectins are lectins that can be associated with the inflammatory process, stimulating or inhibiting the immune system. The objective of this study was to evaluate the in situ expression of TLRs and galectins in radicular cysts and periapical granulomas. METHODS: We analyzed 62 cases (30 radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR-4) and galectins (Gal-3 and Gal-9). RESULTS: The expression of Gal-3 and Gal-9 was significantly higher in periapical granulomas and radicular cysts than in the control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more in periapical granulomas than in radicular cysts. The expression of TLR-2 was significantly higher in periapical granulomas and radicular cysts than in the control group, and it was also significantly higher in radicular cysts with sinus tract than in the cases without sinus tract. Furthermore, the expression of TLR-4 was significantly higher in the cases of periapical granulomas with sinus tract than in the cases without sinus tract. CONCLUSIONS: Gal-3/Gal-9 and TLR-2/TLR-4 expression in the periapical granulomas and radicular cysts is associated with reactive periapical inflammation. Pathobiology of periapical disease is a very complex interplay of many bioactive molecules involved in immunoinflammatory responses. Up-regulation of these bioactive molecules might be an important modulator of inflammatory periapical lesions.


Assuntos
Galectina 3/análise , Galectinas/análise , Granuloma Periapical/metabolismo , Periodontite Periapical/metabolismo , Cisto Radicular/metabolismo , Receptor 2 Toll-Like/análise , Receptor 4 Toll-Like/análise , Biópsia/métodos , Proteínas Sanguíneas , Fístula Dentária/imunologia , Fístula Dentária/metabolismo , Fístula Dentária/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Granuloma Periapical/imunologia , Granuloma Periapical/patologia , Periodontite Periapical/imunologia , Periodontite Periapical/patologia , Cisto Radicular/imunologia , Cisto Radicular/patologia
20.
Nat Prod Res ; 27(20): 1888-95, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23537160

RESUMO

A new triterpene saponin (1) was isolated from a methanol extract of Swartzia apetala Raddi var. glabra, together with the flavonoids mauritianin (2), kaempferol (3) and the triterpene saponin ß-D-glucopyranosyl 3ß-hydroxy-olean-12-en-28-oate (4). These compounds were characterised on the basis of their spectral data, mainly one-dimension (1D; (1)H, (13)C, APT) and two-dimension (2D; (1)H-(1)H-COSY, HMQC and HMBC) nuclear magnetic resonance (NMR) and HR-ESI-MS, and comparison with values in the literature. The analysis by HR-ESI-MS showed a mass compatible with that of triterpene saponin 1. This proposal was supported by molecular modelling. LC-HR-ESI-MS experiment was also used to evaluate the purity of 1 and allowed to speculate about the possibility of the presence of 5 in very small quantity. The extract and four compounds were assayed for antifungal activity against nine strains of Candida spp.


Assuntos
Antifúngicos/isolamento & purificação , Fabaceae/química , Modelos Moleculares , Folhas de Planta/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Antifúngicos/química , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metanol , Estrutura Molecular , Exsudatos de Plantas , Saponinas/química , Triterpenos/química
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