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Using scanning electron microscopy (SEM), six Salsola species from Iran were examined for their epidermis, seed, and fruit micromorphology. Among them were S. brachiata from section Heterotricha, S dendroides, S. incanescens, and S. orientalis from section Caroxylon, S. kali from section Kali, and S. turcomanica from section Physurus. Epidermal cells are divided into three types. There were diamond, irregular, and polygonal cells, as well as straight and undulated walls. Studied species of Salsola have smooth or sculptured fruit surfaces, and there are three main types of fruit surface ornamentation. There is a significant difference between these species based on the type of hair and density of the fruit. Seed shape and color have little systematic significance. The seed epidermis is composed of polygonal, elongated polygonal, irregular, and diamond cells. Although polygonal and irregular testa cells are most common, their size and shape can provide additional information and useful diagnostic characteristics at both specific and infraspecific levels. For taxonomic separation, the current study provides novel insights at micromorphological levels. RESEARCH HIGHLIGHTS: This article reports halophyte are shown as models for adaptation to extreme habitats. These plants are placed among the ecological communities of xerophytes. Here, for the first time, the microstructural analysis of Salsola has been investigated. Additionally, it provides new insights into plant species' response to extreme conditions, as well as possible adaptation strategies at the micromorphological level.
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Background: Cefazolin may minimize the risk of surgical site infection (SSI) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Cefazolin dosing recommendations vary and there is limited evidence for achieved tissue concentrations. Methods: We performed a randomized, controlled, prospective pharmacokinetic pilot study of 12 patients given cefazolin by either intermittent bolus (30 mg/kg every 3 h) or continuous infusion (30 mg/kg bolus followed by 10/mg/kg per hour) during PSF for AIS. Results: Patients were well matched for demographic and perioperative variables. While total drug exposure, measured as area-under-the-curve (AUC), was similar in plasma for bolus and infusion dosing, infusion dosing achieved greater cefazolin exposure in subcutaneous and muscle tissue. Using the pharmacodynamic metric of time spent above minimal inhibitory concentration (MIC), both bolus and infusion dosing performed well. However, when targeting a bactericidal concentration of 32 µg/mL, patients in the bolus group spent a median of 1/5 and 1/3 of the typical 6 h operative time below target in subcutaneous and muscle tissue, respectively. Conclusions: We conclude that intraoperative determination of cefazolin tissue concentrations is feasible and both bolus and infusion dosing of cefazolin achieve concentrations in excess of typical MICs. Infusion dosing appears to more consistently achieve bactericidal concentrations in subcutaneous and muscle tissues.
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AIM: Neonatal mortality (NM) is a significant global challenge that has a profound impact on families, particularly mothers. To address this challenge, the first step is to identify its underlying causes. Accordingly, this study aimed to explore the phenomenon by consulting with stakeholders, including mothers and experts. STUDY DESIGN: This study utilized a qualitative design, conducting in-depth interviews with 16 mothers and 15 healthcare experts to gather information. A conventional content analysis approach was employed to analyze the data. RESULTS: NM is influenced by personal, systemic, and socioeconomic factors. Personal factors can be further divided into those related to the neonate and those related to the mother. Systemic factors are primarily related to the healthcare system, while socioeconomic factors include low literacy, low income, lack of access to healthcare, and consanguineous marriage. CONCLUSION: NM is influenced by a wide range of factors that require separate and targeted interventions to reduce its incidence. In the short term, priority should be given to preventable factors that can be addressed through simple interventions, such as screening mothers for urinary tract infections, educating mothers, and preparing them for pregnancy with necessary lab tests and supplements. In the long term, preventing premature birth, addressing maternal addiction, family poverty, and shortages in healthcare equipment and personnel must be thoroughly addressed.
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Mortalidade Infantil , Mães , Recém-Nascido , Gravidez , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Pesquisa Qualitativa , Atenção à SaúdeRESUMO
To assess bioequivalence of locally acting suspension-based nasal sprays, the U.S. FDA currently recommends a weight-of-evidence approach. In addition to in vitro and human pharmacokinetic (PK) studies, this includes a comparative clinical endpoint study to ensure equivalent bioavailability of the active pharmaceutical ingredient (API) at the site of action. The present study aimed to assess, within an in vitro/in vivo correlation paradigm, whether PK studies and dissolution kinetics are sensitive to differences in drug particle size for a locally acting suspension-based nasal spray product. Two investigational suspension-based nasal formulations of mometasone furoate (MF-I and MF-II; delivered dose: 180 µg) differed in API particle size and were compared in a single-center, double-blind, single-dose, randomized, two-way crossover PK study in 44 healthy subjects with oral charcoal block. Morphology-directed Raman spectroscopy yielded volume median diameters of 3.17 µm for MF-I and 5.50 µm for MF-II, and dissolution studies showed that MF-II had a slower dissolution profile than MF-I. The formulation with larger API particles (MF-II) showed a 45% smaller Cmax and 45% smaller AUC0-inf compared to those of MF-I. Systemic bioavailability of MF-I (2.20%) and MF-II (1.18%) correlated well with the dissolution kinetics, with the faster dissolving formulation yielding the higher bioavailability. This agreement between pharmacokinetics and dissolution kinetics cross-validated both methods and supported their use in assessing potential differences in slowly dissolving suspension-based nasal spray products.
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Sprays Nasais , Humanos , Disponibilidade Biológica , Furoato de Mometasona/farmacocinética , Tamanho da Partícula , Equivalência Terapêutica , Método Duplo-Cego , Estudos Cross-OverRESUMO
The gypsum habitats of Iran are significant reserves of biodiversity containing endemic and rare species. Despite the limited understanding of its characteristics and habitat, it has become essential to study the endemic species of the Semnan gypsic soil. Fresh samples of studied species including Acantholimon cymosum, Astragalus fridae, Astragalus semnanensis, Euphorbia gypsicola, Gypsophila mucronofolia, Moltkia gypsaceae and Nepeta eremokosmus were collected in the wild during the growth season. Leaf surface and leaf cross-sections were considered. The longest hair length was related to A. fridae, A. semnanensis and M. gypsaceae species. The shorter hairs belong to the species A. cymosum, G. mucronofolia and E. gypsicola. Crystals called cystolites were seen in the epidermal cell wall of A. semnanensis leaves. The anatomical characteristics of these species' leaves indicate the presence of dry structures. Using micromorphological studies, we analyzed the hairs of the studied species in terms of their shapes, sizes, and densities. We found some species have hairs with special appendages, which is due to the special conditions in which they have grown. Xeromorphic stomata were found on both leaf surfaces of all endemic gypsophyte plants of Semnan. Several studies have shown that gypsophytes have a specialized mechanism for regulating the absorption of sulfur and calcium from soils containing calcium sulfate or gypsum by their roots. The current study provides novel insights into the response of plant species to extreme conditions and potential adaptation strategies at micromorphological levels.
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Sulfato de Cálcio , Solo , Solo/química , Sulfato de Cálcio/análise , Irã (Geográfico) , Folhas de Planta/anatomia & histologia , Folhas de Planta/química , PlantasRESUMO
This study aimed to gain an in-depth understanding of the pulmonary fate of three experimental fluticasone propionate (FP) dry powder inhaler formulations which differed in mass median aerodynamic diameters (MMAD; A-4.5 µm, B-3.8 µm and C-3.7 µm; total single dose: 500 µg). Systemic disposition parameter estimates were obtained from published pharmacokinetic data after intravenous dosing to improve robustness. A biphasic pulmonary absorption model, with mucociliary clearance from the slower absorption compartment, and three systemic disposition compartments was most suitable. Rapid absorption, presumably from peripheral lung, had half-lives of 6.9 to 14.6 min. The peripherally deposited dose (12.6 µg) was significantly smaller for formulation A-4.5 µm than for the other formulations (38.7 and 39.3 µg for B-3.8 µm and C-3.7 µm). The slow absorption half-lives ranged from 6.86 to 9.13 h and were presumably associated with more central lung regions, where mucociliary clearance removed approximately half of the centrally deposited dose. Simulation-estimation studies showed that a biphasic absorption model could be reliably identified and that parameter estimates were unbiased and reasonably precise. Bioequivalence assessment of population pharmacokinetics derived central and peripheral lung doses suggested that formulation A-4.5 µm lacked bioequivalence compared to the other formulations both for central and peripheral doses. In contrast, the other fomulations were bioequivalent. Overall, population pharmacokinetics holds promise to provide important insights into the pulmonary fate of inhalation drugs, which are not available from non-compartmental analysis. This supports the assessment of the pulmonary bioequivalence of fluticasone propionate inhaled formulations through pharmacokinetic approaches, and may be helpful for discussions on evaluating alternatives to clinical endpoint studies.
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Broncodilatadores , Inaladores de Pó Seco , Humanos , Propionatos , Fluticasona , Pulmão , Administração por Inalação , Androstadienos/farmacocinéticaRESUMO
Melanoma is the major type of skin cancer, which its treatment is still a challenge in the world. In recent years, interest in hibernation-based therapeutic approaches for various biomedical applications has been increased. Many studies indicated that some factors in the blood plasma of hibernating animals such as alpha-2-macroglobulin (A2M) cause anti-proliferative effects. Considering that, the present study was conducted to investigate the anti-cancer effects of hibernating common carp plasma (HCCP) on murine melanoma (B16-F10) in vitro and in vivo. The effect of HCCP on cell viability, migration, apoptosis rate, and cell cycle distribution of B16-F10 cells, tumor growth, and rate of survival were evaluated. To investigate the role of A2M in the anti-cancer effects of HCCP, the gene of interest and proteins in HCCP and non-hibernating common carp plasma (NHCCP) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry analysis. Based on our findings, HCCP significantly decreased B16-F10 cell viability. Moreover, HCCP caused morphological alternations, inhibition of migration, induction of apoptosis, and significantly induced the cell cycle arrest at the G2/M phase. In addition, A2M level was significantly increased in HCCP compared with NHCCP. Taken together, our findings suggested that HCCP had the potential to be a promising novel therapeutic target for cancer treatment because of its anti-cancer properties.
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Carpas , Melanoma Experimental , Animais , Camundongos , Proliferação de Células , Linhagem Celular Tumoral , Melanoma Experimental/patologia , ApoptoseRESUMO
Some commonly used chemicals have teratogenic effects. Perchloroethylene (PCE) is a liquid that is widely used in various industries and drying clothes. In this study, the teratogenic effects of PCE in rat embryos were investigated. In this experimental study, 32 adult Wistar female rats in the weight range of 230-250 g were used. Female rats were randomly divided into 4 groups (n = 8). Control group (without PCE inhalation), experimental group G(I) (exposed to PCE 18 days prior to mating), experimental group G(II) (exposed to PCE 18 days after mating) and experimental group G(III) (exposed to PCE 18 days before and 18 days after mating). Pregnant rats were anesthetized on the 18th day of gestation and then serum and embryos were removed for the required studies. Embryos were examined for number, weight, sex, morphometric parameters of organs, and tissue samples were prepared for histological studies. Serum isolated from dams were evaluated for sexual and gonadal hormones. The results of this study showed that PCE has teratogenic effects on rat embryos. Infertility and reduced birth rate were other effects of PCE in rats. PCE has teratogenic effects and impairs the reproductive system of rats.
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Tetracloroetileno , Gravidez , Humanos , Ratos , Feminino , Animais , Tetracloroetileno/farmacologia , Exposição por Inalação/efeitos adversos , Ratos Wistar , Reprodução , Exposição Materna/efeitos adversosRESUMO
INTRODUCTION AND OBJECTIVES: Despite the use of acetazolamide in the management of CSF leak in most patients after CNS surgeries, there is scant evidence in the literature about the efficacy of this established protocol among adult patients in post-spinal surgery observations. We investigated the potential positive effect of acetazolamide in reducing CSF leak after spine surgery. MATERIALS AND METHODS: We conducted a single-center, double-blind, randomized -controlled trial comparing Oral Acetazolamide plus Corrected body (prone) position (CP+A) versus Corrected body (prone) position alone (CP-A) from January 2014 to September 2015 in the Neurosurgery ward of Shariati Teaching Hospital, Tehran University of Medical Sciences, Tehran, Iran. Seventy-two Patients divided into two groups [CP-A group (nâ¯=â¯36, 50%) and CP+A group (nâ¯=â¯36, 50%)] were randomly assigned to this Clinical Trial study. CP+A group (maintained the 3/4 lateral positionâ¯+â¯dose of acetazolamide 20â¯mg/kg/day in 3-4 divided doses for 7 days), and CP-A group (Control group) (maintained the 3/4 lateral position for 7 days with no acetazolamide). RESULTS: Baseline characteristics between the two groups showed no significant differences: Sex (Pâ¯<â¯.637), Age (Pâ¯<â¯.988) and previous CNS operation at other location besides the spine (Pâ¯<â¯.496). Although we reported post-surgical CSF leak in 2/36 (5.55%) of CP+A group and 4/36 (11.11%) of CP-A (control) group, there was no significant difference observed between the two groups (95%CI, 0.081-2.748; ORâ¯=â¯0.471; Pâ¯<â¯.402; Adjusted Pâ¯<â¯.247). Additionally, no significant differences were observed when we examined surgical characteristics, such as the size of the dural opening (Pâ¯<â¯.489) and type of operation (Pâ¯<â¯.465). CONCLUSION: Acetazolamide has no positive effect in controlling CSF leak after dural opening/dural tear in adult patients who undergo spinal surgery, when we considered alongside the one-week prone position. Therefore, acetazolamide administration may not be essential for postoperative spinal surgery for dural tear. Prospective studies involving a larger sample size may be needed to track long-term acetazolamide complications on patients with CSF leak.
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Acetazolamida , Procedimentos Neurocirúrgicos , Adulto , Humanos , Acetazolamida/uso terapêutico , Estudos Prospectivos , Irã (Geográfico) , Procedimentos Neurocirúrgicos/efeitos adversos , Período Pós-OperatórioRESUMO
Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.
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Antineoplásicos/farmacologia , Carpas , Hibernação , Plasma/química , Plasma/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
The aim of this study was to further evaluate and optimize the Transwell® system for assessing the dissolution behavior of orally inhaled drug products (OIDPs), using fluticasone propionate as a model drug. Sample preparation involved the collection of a relevant inhalable dose fraction through an anatomical mouth/throat model, resulting in a more uniform presentation of drug particles during the subsequent dissolution test. The method differed from previously published procedures by (1) using a 0.4 µm polycarbonate (PC) membrane, (2) stirring the receptor compartment, and (3) placing the drug-containing side of the filter paper face downwards, towards the PC membrane. A model developed in silico, paired with the results of in vitro studies, suggested that a dissolution medium providing a solubility of about 5 µg/mL would be a good starting point for the method's development, resulting in mean transfer times that were about 10 times longer than those of a solution. Furthermore, the model suggested that larger donor/receptor and sampling volumes (3, 3.3 and 2 mL, respectively) will significantly reduce the so-called "mass effect". The outcomes of this study shed further light on the impact of experimental conditions on the complex interplay of dissolution and diffusion within a volume-limited system, under non-sink conditions.
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In the context of streamlining generic approval, this study assessed whether pharmacokinetics (PK) could elucidate the pulmonary fate of orally inhaled drug products (OIDPs). Three fluticasone propionate (FP) dry powder inhaler (DPI) formulations (A-4.5, B-3.8, and C-3.7), differing only in type and composition of lactose fines, exhibited median mass aerodynamic diameter (MMAD) of 4.5 µm (A-4.5), 3.8 µm (B-3.8), and 3.7 µm (C-3.7) and varied in dissolution rates (A-4.5 slower than B-3.8 and C-3.7). In vitro total lung dose (TLDin vitro) was determined as the average dose passing through three anatomical mouth-throat (MT) models and yielded dose normalization factors (DNF) for each DPI formulation X (DNFx = TLDin vitro,x/TLDin vitro,A-4.5). The DNF was 1.00 for A-4.5, 1.32 for B-3.8, and 1.21 for C-3.7. Systemic PK after inhalation of 500 µg FP was assessed in a randomized, double-blind, four-way crossover study in 24 healthy volunteers. Peak concentrations (Cmax) of A-4.5 relative to those of B-3.8 or C-3.7 lacked bioequivalence without or with dose normalization. The area under the curve (AUC0-Inf) was bio-IN-equivalent before dose normalization and bioequivalent after dose normalization. Thus, PK could detect differences in pulmonary available dose (AUC0-Inf) and residence time (dose-normalized Cmax). The differences in dose-normalized Cmax could not be explained by differences in in vitro dissolution. This might suggest that Cmax differences may indicate differences in regional lung deposition. Overall this study supports the use of PK studies to provide relevant information on the pulmonary performance characteristics (i.e., available dose, residence time, and regional lung deposition).
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Broncodilatadores/farmacocinética , Medicamentos Genéricos/farmacocinética , Fluticasona/farmacocinética , Administração por Inalação , Adolescente , Adulto , Aerossóis , Área Sob a Curva , Broncodilatadores/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Liberação Controlada de Fármacos , Medicamentos Genéricos/administração & dosagem , Inaladores de Pó Seco , Feminino , Fluticasona/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Equivalência Terapêutica , Adulto JovemRESUMO
Diabetes mellitus is a chronic metabolic disease associated with high cardiovascular risk. A vascular complication of diabetes is foot ulcers. Diabetic foot ulcers are prevalent and substantially reduce the quality of life of patients who have them. Currently, diabetic foot ulcer is a major problem for wound care specialists, and its treatment requires considerable health care resources. So far, various therapeutic modalities have been proposed to treat diabetic foot ulcers and one of them is stem cell-based therapy. Stem cell-based therapy has shown great promise for the treatment of diabetic foot ulcers. This strategy has been shown to be safe and effective in both preclinical and clinical trials. In this review, we provide an overview of the stem cell types and possible beneficial effects of stem cell transplantation therapy for diabetic foot ulcers, and an overview of the current status of stem cell research in both preclinical and clinical trial stages of treatment strategies for diabetic foot ulcers.
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Muslim women in Iran live in a patriarchal society which significantly restricts their freedom and agency. While there is a growing understanding of social change as it relates to younger Muslim women in Iran, the perspectives and experiences of older women are marginalized; mirroring problems with the intersections of age, gender, and sexuality in the West. In order to address this occlusion, this article draws on life history interviews with 30 older Muslim women living in Tehran and Karaj. Adopting a biographical life course approach, and examining pivotal moments related to sexuality in their lives, we discuss how cultural meanings and symbols of sexuality have emerged and been negotiated by these women at the life stages of puberty, first sex at marriage, and menopause. The patriarchal and religious gender order of Iran transgresses these women's human rights so that sexuality is experienced as a source of shame, stigma, and pollution, yet the women also exert forms of agency in their lives as they adopt and challenge these norms.
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Islamismo , Sexualidade , Idoso , Feminino , Identidade de Gênero , Humanos , Irã (Geográfico) , Comportamento SexualRESUMO
Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p < 0.001). TIL status was a strong independent predictor of DFS in mucinous/mucinous component tumours (HR 0.40, 95% CI 0.23-0.67; p < 0.001), and a superior predictor of prognosis compared with histological grade, MMR and BRAF mutation. Mucinous component and mucinous stage II/III CRCs exhibit clinico-molecular resemblances, with histological grade and BRAF mutation lacking prognostic value. Prognosis for these tumours was instead strongly associated with TIL status, with the most favourable outcomes in TIL-high dMMR tumours, whilst TIL-low tumours had poor outcomes irrespective of MMR status.
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Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Reparo de Erro de Pareamento de DNA , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.
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Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Neuroquímica/educação , Estudantes , Animais , Astrócitos/metabolismo , Congressos como Assunto/tendências , Humanos , Neuroglia/metabolismo , Neurônios/metabolismoRESUMO
Partial regression is common in cutaneous melanoma; however, complete regression manifesting as tumoural melanosis is rare, conceptually challenging and under-reported. In this study we report on clinical, histological and molecular findings in four cases of completely regressed cutaneous melanoma with nodal or brain metastasis, followed by a comprehensive review of the literature. Our series included three women and one man with an average age of 60 years, and clinical presentation with hyper-pigmented cutaneous lesions. The main histological findings were expansile aggregates of melanophages with complete absence of malignant melanocytes on microscopic and immunohistochemical examination of the entire primary skin lesions, as well as substantial reduction in the number of junctional melanocytes in the overlying epidermis. NRAS mutant/BRAF wild type metastatic deposits were identified in three patients, with one patient having a BRAF V600E mutant metastatic tumour. Tumoural melanosis likely represents a partially effective immunological response to melanoma, with complete eradication of cutaneous disease and less effective systemic results. Patients with tumoural melanosis should be managed as potential completely regressed cutaneous melanoma, with comprehensive physical examination, imaging work up and close follow up.
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GTP Fosfo-Hidrolases/genética , Melanoma/patologia , Melanose/patologia , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia , Idoso , Encéfalo/patologia , Feminino , GTP Fosfo-Hidrolases/metabolismo , Humanos , Linfonodos/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/metabolismo , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The occult hepatitis B virus infection (OBI) is a health concern among high-risk groups and immunosuppressed individuals. There is still a paucity of data regarding the occult hepatitis B virus infection among hemophilic patients. With this in mind, we aimed to evaluate the molecular prevalence of OBI among clients with hemophilia. METHODS: Totally, 87 hemophilic patients were selected to be studied. To detect OBI, nested polymerase chain reaction test was used to amplify HBV-S, X, and Core regions. Viral load was determined using an in-house real-time PCR assay. Finally, sequence of S gene was used for genotyping and analysis of mutations. RESULTS: The mean age of patients was 28.4 ± 5.3 years old, with 90.7% of whom were men. HBV-DNA was detected in eight subjects (9.3%). The rate of OBI was much higher in anti-HBs seronegative subjects than that in other patients (P = 0.019). All OBI cases had HBV genotype D, subgenotype D1. In addition, five out of eight cases (62.5%) showed detectable viral loads (a mean viral load of 4.5 × 10 2 copies/mL). sR73H, sI110L, sP120A, sP127T, sQ129H, sG130R, and sC137S were shown to be the most determinant escape mutation and OBI-relevant mutants. CONCLUSION: The rate of OBI among the studied population of hemophilia seems to be remarkable. Therefore, screening for OBI must be a routine practice in patients with hemophilia and also patients undergoing immunosuppressive treatments. Amino acid substitutions were observed in the major hydrophilic region. However further investigations are needed for analysis of exact function.