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1.
BMC Womens Health ; 24(1): 84, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302949

RESUMO

BACKGROUND: Obstetric causes are classified as direct (complications of pregnancy, childbirth or the puerperium) or indirect (caused by pregnancy but not directly caused by it). This study aimed to analyze maternal mortality from obstetric causes in Brazil from 2011 to 2021. METHODS: This was an ecological study on mortality and live births. The outcomes were the specific risk of mortality from direct and indirect cause adjustment and death during pregnancy and the puerperium. Binary and multiple linear logistic regressions were used to assess the influence of sociodemographic factors and maternal and child health indicators on maternal mortality and time of death (pregnancy and puerperium). RESULTS: Regarding mortality during pregnancy and during the puerperium, increased (p = 0.003) and decreased (p = 0.004) mortality over the years, respectively; residing in the northern region was associated with lower (p < 0.05) and greater (p = 0.035) odds; and the Maternal Mortality Committee was the primary and least active source of investigation, respectively (p < 0.0001). The number of deaths from indirect causes increased with age (p < 0.001) and in the northern region (p = 0.011) and decreased in the white (< 0.05) and stable union (0.002) regions. Specifically, for mortality risk, the age group [women aged 15-19 years presented an increase in cesarean section (p < 0.001) was greater than that of women who had < 4 antenatal visits (p < 0.001)], education [women who completed high school (8 to 11 years) was greater when they had < 4 prenatal visits (p = 0.018)], and marital status [unmarried women had more than 4 antenatal visits (p < 0.001); cesarean birth (p = 0.010) and < 4 antenatal visits (p = 0.009) were predictors of marriage; and women in a stable union who had < 4 prenatal visits and live births to teenage mothers (p < 0.001) were predictors]. Women who had no education (p = 0.003), were divorced (p = 0.036), had cesarean deliveries (p < 0.012), or lived in the north or northeast (p < 0.008) had higher indirect specific mortality risk. CONCLUSIONS: Sociodemographic factors and maternal and child health indicators were related to different patterns of obstetric mortality. Obstetric mortality varied by region, marital status, race, delivery, prenatal care, and cause of death.


Assuntos
Mortalidade Materna , Complicações na Gravidez , Adolescente , Criança , Gravidez , Feminino , Humanos , Cesárea , Brasil/epidemiologia , Cuidado Pré-Natal
2.
Parasite Immunol ; 45(3): e12966, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36601688

RESUMO

The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.


Assuntos
Leishmania , Leishmaniose Cutânea , Humanos , Linfócitos T Reguladores , Antígeno CTLA-4 , Leucócitos Mononucleares , Receptores CCR7 , Antígeno Ki-67 , Fatores de Transcrição Forkhead
3.
Childs Nerv Syst ; 39(7): 1773-1782, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609513

RESUMO

OBJECTIVES: This study aimed to verify possible associations between sociodemographic and clinical factors in live births with spinal dysraphism. METHODS: An analytical (descriptive and inferential) and ecological study was carried out based on secondary data of 11,308 live births with spinal dysraphism registered in the Live Birth Information System (SINASC) in Brazil from 1999 to 2019. Demographic factors analyzed were age, education, mothers' marital status and geographic region. The clinical factors analyzed were duration, gestation period, birthweight, and number of prenatal visits performed by women who underwent medical follow-up. RESULTS: There was an increase in the number of cases of spinal dysraphism in recent years in Brazil with an annual percentage variation of 3.52%. However, the period from 2005 to 2009 showed a reduction in live births with spinal dysraphism. The regions with the highest incidence were the South and Southeast. The risk increased in mothers born after 1980, older than 30 years and with a high level of education. The risk was increased in live births of whites and blacks, born from double pregnancy and with body weight less than 3000 g. The absence of prenatal care was associated with a higher incidence. CONCLUSION: Sociodemographic and clinical factors have specific characteristics that can predict spinal dysraphism in newborns in Brazil.


Assuntos
Defeitos do Tubo Neural , Disrafismo Espinal , Gravidez , Recém-Nascido , Feminino , Humanos , Nascido Vivo/epidemiologia , Brasil/epidemiologia , Disrafismo Espinal/epidemiologia , Incidência
4.
Exp Mol Pathol ; 124: 104734, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34914974

RESUMO

OBJECTIVE: High-grade cervical lesions (HSIL) are associated with the presence of high-risk HPV types, tissue expression of p16, and increased chance of malignant progression, requiring surgical intervention. To improve risk evaluation, we assessed the discriminatory power of the histological findings associated with p16 immunohistochemistry (IHC) staining to classify the low-grade cervical lesion (LSIL) and HSIL. METHODS: We collected cervical biopsies from colposcopy-visible lesions and non-affected tissue (adjacent to the lesions) of 62 Brazilian women and labeled them with anti-p16 antibodies. In addition to the observational pattern and labeling to define the latent classes (affected vs. non-affected), a computational tool was used for semi-quantitative analysis of p16 expression. The intensity of staining of the nucleus or cytoplasm was captured using the Gimp 2.10 software. ROC curves were used to determine cutoff values for p16 expression in patients classified as LSIL and HSIL by latent class statistics for each labeling stratum. RESULTS: p16 nuclear labeling showed the best sensitivity and specificity to discriminate LSIL with low p16 expression (62%) and HSIL with high p16 expression (37%). Many patients whose lesions had intermediate levels of p16 nuclear staining were subsequently stratified according to the expression of p16 in the cytoplasm, indicating that five of 21 LSIL were at risk of progression, and 13 of 41 HSIL at risk of regression. CONCLUSIONS: We suggest a hierarchical analysis, with histology at the first level, followed by a labeling analysis in the nucleus and then in the cytoplasm to increase the accuracy of the HPV cervical lesion stratification.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/análise , Medição de Risco , Displasia do Colo do Útero , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Brasil , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia
5.
BMC Pediatr ; 22(1): 560, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151512

RESUMO

BACKGROUND: The 5-minute APGAR score is clinically used as a screening tool to assess how the newborn has reacted to previous care, remaining relevant for predicting neonatal survival. This study aimed to analyze the determinants of the 5th minute APGAR score, and the factors associated with the death and survival of newborns with low APGAR scores hospitalized in the neonatal intensive care unit (NICU) at a referral public hospital in North Brazil. METHODS: This was a hospital-based retrospective case-control study with 277 medical records. Newborns who presented with a 1-minute APGAR score < 7 followed by a 5-minute APGAR score < 7 were considered cases, while a score ≥ 7 was categorized as controls. Univariate and multivariable logistic regression analyses were used to establish the determinant factors of the low APGAR score and death outcome in this group. Survival curves were obtained using the Kaplan-Meier estimator, and then univariate and multivariate Cox regression was performed. RESULTS: After adjusted analysis, the factor associated with low APGAR scores was vaginal delivery (OR = 3.25, 95%CI = 1.60-6.62, p = 0.001). Birth injury (OR = 0.39, 95%CI = 0.19-0.83, p = 0.014) was associated with upper APGAR scores. No significant independent associations were observed between the variables analyzed and death in the low APGAR score group. The Kaplan-Meier curve showed that individuals who presented Cesarean delivery had a shorter survival time in the ICU. CONCLUSION: In this setting, a 5-minute Apgar score < 7 was associated with the occurrence of vaginal delivery and birth injury with a 5-minute Apgar score ≥ 7. Survival in ICU was lower in newborns that were delivered via cesarean section.


Assuntos
Traumatismos do Nascimento , Doenças do Recém-Nascido , Índice de Apgar , Estudos de Casos e Controles , Cesárea , Feminino , Humanos , Recém-Nascido , Terapia Intensiva Neonatal , Gravidez , Estudos Retrospectivos
6.
Planta Med ; 86(6): 395-404, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32168547

RESUMO

Echinodorus grandiflorus is a semiaquatic plant native to Brazil and belongs to the Alismataceae family. Infusion preparations of the leaves of this plant are often used due to its diuretic, blood pressure lowering, and anti-inflammatory properties. Our aim was to investigate the effects of chronic treatment with the crude hydroalcoholic extract of E. grandiflorus on central and peripheral microvascular changes induced in a model of hypertension and diabetes. The hemodynamic and microvascular effects of E. grandiflorus extract (50, 100, or 200 mg/kg/day for 28 days) or the isolated major diterpene from E. grandiflorus (3 to 10 mg/kg i. v.) were evaluated in spontaneously hypertensive rats using tail plethysmography and intravital fluorescence videomicroscopy, respectively, and were compared to vehicle-treated normotensive Wistar-Kyoto rats. We also investigated the protective effects of chronic treatment with E. grandiflorus (100 mg/kg/day) in brain capillary density and leukocyte-endothelium interactions on the brain vessels of DM-spontaneously (DM: diabetes mellitus) hypertensive rats. Chronically treating spontaneously hypertensive rats with increasing doses of crude hydroalcoholic E. grandiflorus extract resulted in significant dose-dependent reductions in systolic blood pressure and an anti-inflammatory effect on the brain microcirculation of DM-spontaneously hypertensive rat animals. Using laser speckle contrast imaging, we observed that intravenous administration of the major isolated clerodane diterpene metabolite (1 - 10 mg/kg) increased microvascular blood flow by 25% in spontaneously hypertensive rat skeletal muscle. The results of this study show that E. grandiflorus extracts can be useful in the prevention and reduction of microcirculatory damage in arterial hypertension and other diseases that involve microvascular dysfunction.


Assuntos
Alismataceae , Hipertensão , Animais , Pressão Sanguínea , Brasil , Microcirculação , Extratos Vegetais , Folhas de Planta , Ratos
7.
Am J Pathol ; 188(11): 2674-2687, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30121257

RESUMO

Toxoplasmosis is one of the leading parasitic diseases worldwide. Some data suggest that chronic acquired toxoplasmosis could be linked to behavioral alterations in humans. The parasite infects neurons, forming immunologically silent cysts. Cerebral microcirculation homeostasis is determinant to brain functions, and pathologic states can alter capillarity or blood perfusion, leading to neurodegeneration and cognitive deficits. Albino mice were infected with Toxoplasma gondii (ME49 strain) and analyzed after 10, 40, and 180 days. Infected mice presented decreased cerebral blood flow at 10 and 40 days post infection (dpi), which were restored at 180 dpi, as shown by laser speckle contrast imaging. Intravital microscopy demonstrated that infection led to significant capillary rarefaction, accompanied by neuroinflammation, with microglial activation and increased numbers of rolling and adherent leukocytes to the wall of cerebral capillaries. Acetylcholine-induced vasodilation was altered at all time points, and blood brain barrier permeability was evident in infected animals at 40 dpi. Infection reduced angiogenesis, with a decreased number of isolectin B4-stained blood vessels and a decrease in length and branching of laminin-stained capillaries. Sulfadiazine reduced parasite load and partially repaired microvascular damages. We conclude that T. gondii latent infection causes a harmful insult in the brain, promoting neuroinflammation and microcirculatory dysfunction in the brain, with decreased angiogenesis and can contribute to a neurodegenerative process.


Assuntos
Barreira Hematoencefálica/patologia , Endotélio Vascular/patologia , Inflamação/patologia , Microcirculação , Neurônios/patologia , Toxoplasma/patogenicidade , Toxoplasmose Cerebral/patologia , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/parasitologia , Endotélio Vascular/imunologia , Endotélio Vascular/parasitologia , Feminino , Inflamação/imunologia , Inflamação/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/imunologia , Neurônios/parasitologia , Toxoplasmose Cerebral/imunologia , Toxoplasmose Cerebral/parasitologia
8.
Inflamm Res ; 67(1): 43-55, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29151155

RESUMO

OBJECTIVE: Chronic inflammation has been recognized as having a prominent role pathogenesis of benign prostatic hyperplasia (BPH) and cancer. It is believed that chronic inflammation induces prostatic fibromuscular growth. This correlation has been clearly illustrated by both in vivo and in vitro studies; however, current experimental models of BPH require complex surgery or hormonal treatment. Therefore, the aim of the present study was to propose a new murine model of BPH/prostatitis induced by intraurethral injection of LPS. METHODS: Male Swiss and C57Bl/6 mice were then sacrificed 3, 7, 10, and 14 days after intraurethral injection of LPS. The prostates were quickly dissected and fixed for morphological and immunohistochemical analyses. RESULTS: The results showed that LPS played an important role in the cell proliferation of the prostate. Histological and ultrastructural analysis showed epithelial hyperplasia, clear stromal cells, little inflammatory infiltration, and heavy bleeding. Treatment with LPS also promoted the increase of growth factor (FGF-7 and TGF-ß), α-actin, and proinflammatory cytokines (IL-1, IL-6, IL-17), both in the stroma and epithelium. CONCLUSION: According to the present findings, it can be concluded that the intraurethral administration of LPS promotes tissue remodeling, as well as stimulating the pattern of pro-inflammatory cytokines, and therefore, constitutes an effective experimental model of BPH/inflammation.


Assuntos
Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Fator 7 de Crescimento de Fibroblastos/imunologia , Inflamação/imunologia , Inflamação/patologia , Injeções , Masculino , Camundongos Endogâmicos C57BL , Próstata/imunologia , Próstata/patologia , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/patologia , Uretra
9.
BMC Neurosci ; 18(1): 67, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28886695

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS. RESULTS: We examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery. Microvascular blood flow was evaluated on the parietal cortex surface through a cranial window by laser speckle contrast imaging, functional capillary density, endothelial function and endothelial-leukocyte interactions by intravital videomicroscopy. Lipid peroxidation was assessed by TBARs analysis, the expression of oxidative enzymes and inflammatory markers in the brain tissue was analyzed by real-time PCR. The cerebral IR in MetS animals induced a functional capillary rarefaction (HFD IR 117 ± 17 vs. CTL IR 224 ± 35 capillary/mm2; p < 0.05), blunted the endothelial response to acetylcholine (HFD IR -16.93% vs. CTL IR 16.19% from baseline inner diameter p < 0.05) and increased the endothelial-leukocyte interactions in the venules in the brain. The impact of ischemia on the cerebral microvascular blood flow was worsened in MetS animals, with a marked reduction of cerebral blood flow, exposing brain tissue to a higher state of hypoxia. CONCLUSIONS: Our results demonstrate that during ischemia and reperfusion, animals with MetS are more susceptible to alterations in the cerebral microcirculation involving endothelial dysfunction and oxidative stress events.


Assuntos
Isquemia Encefálica/fisiopatologia , Dieta Hiperlipídica , Síndrome Metabólica/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Circulação Cerebrovascular/fisiologia , Microcirculação/fisiologia , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reperfusão/métodos
10.
Toxicol Appl Pharmacol ; 333: 92-99, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28851623

RESUMO

The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28/DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA). Echocardiography analysis demonstrated an increase in the pulmonary arterial blood flow gradient and velocity in the systole and RV area in the MCT28 group, while treatment with DEC resulted in a significant reduction in these parameters. Deposition of collagen fibers and αSMA staining around the pulmonary arteries was evident in the MCT28 group, while treatment with DEC reduced both. Western blot analysis revealed a decrease in BMPR2 in the MCT28 group, in contrast DEC treatment resulted in a significant increase in the level of BMPR2. DEC also significantly reduced the level of VEGF compared to the MCT28 group. Apoptosis extrinsic and intrinsic pathway markers were reduced in the MCT28 group. After treatment with DEC these levels returned to baseline. The results of this study indicate that DEC attenuates PH in an experimental monocrotaline-induced model by inhibiting a series of markers involved in cell proliferation/death.


Assuntos
Dietilcarbamazina/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Actinas/genética , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Colágeno Tipo I/genética , Dietilcarbamazina/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/tratamento farmacológico , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Monocrotalina , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Função Ventricular Esquerda/efeitos dos fármacos
11.
Int J Eat Disord ; 50(7): 793-800, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28301060

RESUMO

OBJECTIVE: The aim of this study was to examine the point prevalence of eating disorders and picking/nibbling in elderly women. METHODS: This was a two-stage epidemiological study that assessed 342 women aged 65-94 years old. In Stage 1, the following screening measures were used to identify possible cases: the Mini-Mental State Examination, to screen and exclude patients with cognitive impairment; Weight Concerns Scale; SCOFF (Sick, Control, One, Fat, Food) Questionnaire; Eating Disorder Examination Questionnaire-dietary restraint subscale; and three questions to screen for picking/nibbling and night eating syndrome. Women selected for Stage 2 (n = 118) were interviewed using the diagnostic items of the Eating Disorder Examination. RESULTS: According to the DSM-5, the prevalence of all eating disorders was 3.25% (1.83-5.7, 95% C.I.). Prevalence of binge-eating disorder was 1.68% (0.82-3.82, 95% C.I.), of other specified feeding or eating disorders was 1.48% (0.63-3.42, 95% C.I.), and of bulimia nervosa 0.3% (.05-1.7, 95% C.I.)]. Binge-eating episodes were reported by 5.62% of women. No cases of anorexia nervosa or night eating syndrome were identified. The prevalence of picking/nibbling was 18.9%. Picking/nibbling was associated with increased body mass index (t(322) = -3.28, p < .001) and binge-eating episodes (χ2 (1) = 5.65, p < .017). DISCUSSION: Prevalence rates of eating disorders on elderly Portuguese women were comparable to those found on young women. Our data support the literature that suggests that binge-eating disorder is particularly prevalent in older adults. Picking/nibbling was the most prevalent eating behavior and we provide further evidence for its association with weight and disordered eating.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dieta , Feminino , Humanos , Prevalência , Inquéritos e Questionários
12.
Microcirculation ; 23(4): 320-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27086551

RESUMO

OBJECTIVES: The objective of this study was to investigate the role of the SNS on hemodynamic, metabolic, and microvascular alterations in a rat model of HFD-induced MS with salt supplementation. METHODS: In total, 40 adult male Wistar rats were fed normal chow (n = 10) or a HFD (n = 30) for 20 weeks. Thereafter, the HFD group received the centrally acting sympatho-modulatory drugs clonidine (0.1 mg/kg) or rilmenidine (1 mg/kg) or vehicle (n = 10/group) orally by gavage. FCD was evaluated using intravital video microscopy, and the SCD was evaluated using histochemical analysis. RESULTS: The pharmacological modulation of the SNS induced concomitant reductions in SBP, HR and plasma catecholamine levels. These effects were accompanied by a reversal of functional and structural capillary rarefaction in the skeletal muscle in both treated groups and an increase in SCD in the left ventricle only in the rilmenidine group. Improvement of the lipid profile and of glucose intolerance was also obtained only with rilmenidine treatment. CONCLUSIONS: Modulation of sympathetic overactivity results in the reversal of microvascular rarefaction in the skeletal muscle and left ventricle and improves metabolic parameters in an experimental model of MS in rats.


Assuntos
Dieta Hiperlipídica , Síndrome Metabólica/etiologia , Microvasos/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Simpatolíticos/farmacologia , Agonistas alfa-Adrenérgicos , Animais , Clonidina/farmacologia , Microscopia Intravital , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Oxazóis/farmacologia , Ratos , Ratos Wistar , Rilmenidina , Cloreto de Sódio na Dieta/farmacologia , Simpatolíticos/uso terapêutico
13.
Clin Exp Pharmacol Physiol ; 42(4): 369-79, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25676413

RESUMO

Alcoholic liver disease is a major cause of chronic liver disease worldwide. Diethylcarbamazine (DEC) is a drug that has anti-inflammatory properties due to its effects on the metabolism of arachidonic acid. The present study examined the anti-inflammatory effects of DEC on the mechanisms of alcoholic liver disease. C57BL/6 mice were divided into seven groups: (i) control; (ii) DEC 50 mg/kg; (iii) alcohol; (iv) alcohol + DEC 50 mg/kg; (v) alcohol + celecoxib 50 mg/kg; (vi) alcohol + pyrrolidine dithiocarbamate 100 mg/kg; and (vii) alcohol + pyrrolidine dithiocarbamate 100 mg/kg + DEC 50 mg/kg. Liver fragments were stained with haemotoxylin-eosin and Sirius red, and processed for immunofluorescence, western blot, and immunohistochemistry. Serum was also collected for biochemical measurements. Alcohol induced liver damage, elevated collagen content, and increased expression of nuclear factor kappa-light-chain-enhancer of activated B cells and inflammatory markers (tumour necrosis factor-α, interferon-γ, interleukin-1ß, inducible nitric oxide synthase, cyclooxygenases-2, and transforming growth factor-ß). Treatment with DEC was able to reduce liver damage, collagen content, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells and inflammatory markers; it also ameliorated biochemistry parameters (total cholesterol, high-density lipoprotein cholesterol, triglyceride content and aspartate aminotransferase) and increased the expression of anti-inflammatory markers (p-5' adenosine monophosphate-activated protein kinase and interleukin-10). Future clinical trials may demonstrate that oral administration of DEC may be suitable for the treatment of alcoholic liver disease and other liver diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Dietilcarbamazina/farmacologia , Cirrose Hepática Alcoólica/tratamento farmacológico , Fígado/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Aspartato Aminotransferases/sangue , Colágeno/metabolismo , Ciclo-Oxigenase 2/genética , Citocinas/metabolismo , Citoproteção , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
14.
Wound Repair Regen ; 22(5): 640-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25039304

RESUMO

The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5-azacytidine on wound healing in rats. 5-Azacytidine decreases the expression of follistatin-1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight-week-old male Wistar rats were submitted to 8.0-mm punch-wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5-azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5-azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5-Azacytidine treatment also resulted in increased gene expression of transforming growth factor-beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor-alpha and interleukin-10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5-azacytidine, most of the beneficial effects of the drug were lost. Thus, 5-azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents.


Assuntos
Azacitidina/farmacologia , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Folistatina/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Ativinas/efeitos dos fármacos , Administração Cutânea , Animais , Expressão Gênica/efeitos dos fármacos , Interleucina-10/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinas/efeitos dos fármacos , Queratinas/metabolismo , Masculino , Precursores de Proteínas/efeitos dos fármacos , Precursores de Proteínas/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
15.
Mediators Inflamm ; 2014: 105120, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24550603

RESUMO

Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor-α and increased expression of interleukin-1ß, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-κB. The oral administration of DEC (50 mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation.


Assuntos
Carragenina/efeitos adversos , Dietilcarbamazina/química , Regulação da Expressão Gênica/efeitos dos fármacos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Administração Oral , Animais , Anti-Inflamatórios/química , Ciclo-Oxigenase 2/metabolismo , Inflamação , Interleucina-1beta/metabolismo , Leucócitos/efeitos dos fármacos , Inibidores de Lipoxigenase/química , Pulmão/metabolismo , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Pleurisia/induzido quimicamente , Distribuição Aleatória
16.
Cancers (Basel) ; 16(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610950

RESUMO

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

17.
J Public Health Res ; 12(1): 22799036221150062, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36686587

RESUMO

Background: The aim of this study was to analyze the influence of sociodemographic and clinical variables as determinants of mortality and survival in patients with ST-segment elevation acute myocardial infarction in the Eastern Amazon. Design and methods: This observational, longitudinal, and retrospective study was conducted at the Gaspar Vianna Clinical Hospital Foundation in patients hospitalized from January 2017 to June 2020. Patients were divided into two groups: those who survived (G1) (n = 646) and those who died (G2) (n = 37). Sociodemographic and clinical variables associated with mortality and survival in these two groups were analyzed. Results: Patients with STEMI who had the highest risk of death were often the oldest (G1: 61.58 ± 10.74 years; G2: 69.57 ± 9.02 years; t = -4.492; p = 0.001), with Killip III-IV classifications (OR = 0.13; 95% CI = 0.02-0.71; p = 0.03), and with diseases such as heart failure (OR = 0.07; 95% CI = 0.004-1.50; p = 0.168) or renal failure (OR = 0.03; 95% CI = 0.006-0.16; p = 0.0001). In addition, female sex (hazard ratio = 2.073; 95% CI = 1.413-5.170), Killip III-IV classifications (hazard ratio = 4.041; 95% CI = 1.703-18.883) and the presence of heart failure (hazard ratio = 34.102; 95% CI = 4.410-263.684) or renal failure (hazard ratio = 14.278; 95% CI = 3.275-62.248) shortened in-hospital survival. Conclusions: Specific sociodemographic and clinical aspects influenced mortality and survival in patients with acute ST -elevation myocardial infarction.

18.
Behav Sci (Basel) ; 13(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37366744

RESUMO

Quilombola communities are descended from African slaves who escaped in resistance to imperial rule in Brazil. Today, these communities suffer from inadequate health care and health promotion programs due to socioeconomic, geographic, and political factors. This generates greater vulnerability among these groups because they have limited information about prevention to improve their quality of life. This research aimed to analyze the sexuality of young quilombola adults and the impact on their quality of life through an observational, cross-sectional, quantitative study with descriptive and inferential analyses. Our study is the first to address these issues among quilombolas in the Eastern Amazon region. The participants were 79 individuals of both sexes, aged between 18 to 35 years, belonging to seven communities in the state of Pará. The questionnaires were designed to assess sexual behavior and satisfaction, values and beliefs about sexuality, prejudice regarding sexual and gender diversity, knowledge about sexually transmitted infections (STIs), beliefs about maternity, and quality of life. Women reported greater sexual dissatisfaction and lower quality of life than men. Men reported no dysfunctions; however, they were highly prejudiced towards sexual and gender diversity. Low education negatively impacts the health of quilombola populations, as knowledge about STIs and values and beliefs influence sexual behavior, exposing individuals to diseases. The research also confirms that, both among quilombolas and other groups, factors such as sexual satisfaction, values and beliefs about reproduction, and affectivity directly influence the quality of life.

19.
Int J Breast Cancer ; 2023: 6665725, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936925

RESUMO

Background: Breast cancer mortality is increasing in Brazil. This study examines the impact of sociodemographic factors, screening procedures, and primary healthcare (PHC) on breast cancer mortality. Methods: An ecological study analyzed secondary data of women diagnosed with breast cancer who died between 2000 and 2019. Sociodemographic factors, screening procedures, and PHC were examined in relation to breast cancer mortality. Statistical analyses included normality tests, Kruskal-Wallis and one-way ANOVA tests with post hoc comparisons, Pearson and Spearman correlation tests, age-period-cohort analysis, Kaplan-Meier analysis, and Cox regression analysis. Significance was set at p < 0.05. Results: Mortality rates were higher in the southeast (15.77) and south (15.97) regions compared to the north (5.07) (p < 0.0001). Survival rates were longer in the southeast (70.3 ± 0.05) and south (70.6 ± 0.09) than in the north (63.98 ± 0.053) (p ≤ 0.001). Mortality increased with age after 32 years (p ≤ 0.001). Brown and indigenous women had lower mortality and survival rates. Increased coverage of PHC, ultrasound, and biopsy did not reduce mortality. However, improved cytopathologic analysis led to a decrease in mortality. Conclusions: Sociodemographic factors, screening procedures, and PHC are specific predictors of breast cancer mortality in Brazil.

20.
Cancers (Basel) ; 15(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37627177

RESUMO

Testicular cancer is common in young men, and early detection and multimodality treatment can lead to successful outcomes. This study aims to identify sociodemographic and risk factors associated with higher testicular cancer mortality and poorer survival rates, while examining the impact of diagnostic and treatment procedures on reducing mortality. The retrospective ecological study analyzed mortality data from testicular cancer in Brazil from 2001 to 2020. Sociodemographic variables such as marital status, age, birth period, year of death (cohort), race, and geographic region were assessed. Risk factors included cryptorchidism and pesticide exposure. Data were subjected to statistical analysis, which revealed an increasing trend in mortality after 2011 among persons born after 1976 in the 15-40 age group. Individuals in the South Region, whites, and singles had higher age-standardized mortality rates (ASMRs), while singles had lower survival rates. The Northeast region had a higher survival rate. Fungicides and insecticides increase ASMR in Brazil. Herbicides increase ASMR in the Northeast and Midwest regions and insecticides increase ASMR in the Northeast, Southeast, and Midwest regions. High rates of implementation of diagnostic procedures in the Midwest were not sufficient to reduce ASMR. No treatment procedure was associated with mortality at the national or regional level.

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