RESUMO
Although extremely rare, uterine damage after hysteroscopic myomectomy sets the precondition for various life-threatening placental attachment disorders like placenta percreta (PP) or scar pregnancy. Due to vast clinical similarities, these terms are often used interchangeably. We report a case of a 47-yr-old patient at 27 wk + 4 d of gestation who presented with rectal bleeding. Clinical history revealed a previous uterine posterior wall myomectomy. The patient received intensive diagnostic work-up including sonography and magnetic resonance imaging. Under the suspicion of a bleeding Meckel diverticulum, an emergency laparotomy was performed. Intraoperatively it was observed that the placental tissue infiltrated the small bowel intestine at the location of the previous myomectomy. The adjacent intestine and the infiltrating placenta were surgically removed. The placenta could be easily detached from the uterus, which is why no hysterectomy was performed. Retrospectively, no radiologic or clinical hints of PP or scar pregnancy were evident before the surgery. Moreover, the pathologic work-up carried out afterwards proved no histopathologic evidence for PP. Our case underlines several clinical and pathologic difficulties. First, invasive placenta disorders including infiltration of intestinal organs have to be considered even after minor surgical interventions such as myomectomy. Second, clinical presentation is extremely variable and sometimes misleading, depending on the localization and the type of invasion. Our case underlines the importance of histopathologic work-up for distinguishing between various placenta attachment disorders such as PP and scar pregnancy. Given the large overlap in clinical presentation, pathophysiology and definition, we propose that the current definitions for PP and scar pregnancy have to be carefully reevaluated and broadened.
Assuntos
Placenta Acreta , Miomectomia Uterina , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Feminino , Humanos , Intestinos/patologia , Pessoa de Meia-Idade , Placenta/patologia , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/cirurgia , Gravidez , Estudos Retrospectivos , Miomectomia Uterina/efeitos adversosRESUMO
BACKGROUND: Natural rubber latex (NRL) allergy is commonly diagnosed according to medical history, skin allergy tests, and serological analyses. However, skin tests are increasingly being abandoned because of (i) their time-consuming nature, (ii) latex preparations for skin tests being not commercially available, and (iii) the use of in-house prepared test solutions is becoming ever more difficult due to increasing regulatory hurdles. In this light, we have evaluated differences in the profiles of current and former patients with suspected latex allergy. METHODS: Sera of skin test-positive patients from a historic cohort (1995-2001, n = 149 patients) and currently (2014-2015, n = 48 patients) were simultaneously analyzed for specific IgE to latex by ImmunoCAP. If the serological screening was positive (≥0.35 kU/L), component-resolved diagnostics including profilins and cross-reactive carbohydrate determinants (CCDs) were performed. RESULTS: In contrast to 88% (131/149) of the skin test-positive patients from the 1990s, only 51.1% (24/47) of the current cohort were found positive for specific IgE to latex. While 48.3% (72/149) of the patients had a convincing positive history in the 1990s, current skin test-positive patients rarely reported a relevant medical history (8.5%, 4/47). Specific IgE levels to latex were significantly higher in former patients with suspected latex allergy (p < 0.001) than in former sensitized individuals without allergy. However, this significant difference was lost in current allergic and sensitized patients with positive skin tests. CONCLUSION: Sensitization profiles in patients with latex allergy have changed significantly over the last 2 decades. Discrimination between NRL sensitization and clinical allergy remains a diagnostic challenge. Our data highlight the need for a combination of all 3 criteria, i.e., patient history, skin test, and analysis of specific IgE, for a correct diagnosis of latex allergy.
Assuntos
Alérgenos/imunologia , Hipersensibilidade ao Látex/epidemiologia , Hipersensibilidade ao Látex/imunologia , Látex/efeitos adversos , Especificidade de Anticorpos/imunologia , Reações Cruzadas/imunologia , Feminino , Humanos , Imunização , Imunoglobulina E/imunologia , Hipersensibilidade ao Látex/diagnóstico , Masculino , Prevalência , Testes CutâneosRESUMO
As a progressive neuropathic condition, glaucoma can cause lifelong blindness if left untreated. Novel phenylpyridazine-tethered sulfonamides were designed as selective inhibitors for carbonic anhydrase (CA) isoform II to find effective therapeutic agents for glaucoma. Subsequently, the target inhibitors were synthesized and assessed for their inhibitory action against cytosolic CA I and II. Interestingly, the synthesized molecules poorly inhibited CA I while exhibiting low subnanomolar potency against CA II. Compound 7c disclosed the most potent activity (IC50 = 0.63 nM) with high selectivity against CA II (605-fold than acetazolamide selectivity). Moreover, compound 7c also showed significant in vivo IOP-reducing properties in the in vivo model of glaucoma. Furthermore, the binding of compound 7c to CA II was assessed at the molecular level, exploiting the molecular docking approach.
Assuntos
Glaucoma , Sulfonamidas , Humanos , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Sulfonamidas/química , Anidrase Carbônica II , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/uso terapêutico , Inibidores da Anidrase Carbônica/química , Estrutura Molecular , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Glaucoma/tratamento farmacológico , Sulfanilamida , Anidrase Carbônica IX/metabolismoRESUMO
MAPK pathway sparkles with RTK activation, passes through subsequent downstream RAS-RAF-MEK-ERK signaling cascades, with consequent direct and indirect CDK4/6 signaling activation, and ends with cell survival, division, and proliferation. However, the emergence of anomalies such as mutations or overexpression in one or more points of the pathway could lead to cancer development and drug resistance. Therefore, designing small inhibitors to strike multitudinous MAPK pathway steps could be a promising synergistic strategy to confine cancer. In this study, twelve 6-indolylpyridone-3-carbonitrile candidates were synthesized and assessed in vitro for antineoplastic activity using four cancer cell lines. The initial antiproliferative screening revealed that compounds 3g, 3h, and 3i were the most potent candidates (GI% Avg = 70.10, 73.94, 74.33%, respectively) compared to staurosporine (GI% Avg = 70.99%). The subsequent safety and selectivity assessment showed that 3h exhibited sub-micromolar inhibition against lung cancer cells (HOP-92 GI50 = 0.75 µM) and 13.7 times selectivity toward cancerous cells over normal cells. As a result, 3h was nominated for deep mechanistic studies which evidenced that compound 3h impressively blocks multiple keystones of the MAPK pathway with nanomolar potency (EGFRWT IC50 = 281 nM, c-MET IC50 = 205 nM, B-RAFWT IC50 = 112 nM, and CDK4/6 IC50 = 95 and 184 nM, respectively). Surprisingly, 3h showed a remarkable potency against mutated EGFR and B-RAF, being 4 and 1.3 more selective to the mutated enzymes over the wild-type forms (EGFRT790M IC50 = 69 nM and B-RAFV600E IC50 = 83 nM). Ultimately, combined molecular docking and molecular dynamics (MD) calculations were executed to inspect the mode of binding and the complex stability of 3h towards the keystones of the MAPK pathway.
Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Receptores ErbB , Proliferação de Células , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/química , Mutação , Antineoplásicos/química , Proteínas Proto-Oncogênicas B-raf , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Heavy metal removal by waste material from different industry has become one of the main economical approaches for zero waste industrial activity. Therefore, iron oxide fine waste by-product from steel industry was converted into nanoparticulates (Fe2O3 NPs) and further crosslinked with starch as a good stabilizer and biodegradable polymer using formaldehyde to form Fe2O3 NPs-Starch nanocomposite. The scanning electron microscope (SEM) showed the average particle size (40-70â¯nm). The sorption behavior of this nanocomposite was investigated using Pb(II), Hg(II) and Cd(II). Different factors such as solution pH, contact time, nanocomposite dosage and metal concentration were monitored to determine the adsorptive capacity. Langmuir, Temkin, Freundlich and Dubinin-Radushkevich models were employed to study the adsorption isotherms. The maximum sorption capacities were 2000â¯mgâ¯g-1 for Pb(II), 133.3â¯mgâ¯g-1 for Hg(II) and 322.58â¯mgâ¯g-1 for Cd(II). The results referred that Hg(II) and Cd(II) were best fitted by all models except Pb(II) obeyed the Freundlich isotherm model only. The Fe2O3 NPs-Starch nanocomposite emphasized its potential application as a sustainable low cost nanocomposite for metals extraction from tap water, marine water and industrial wastewater with percentage recovery 93-97%, 70-94% and 76-93%, respectively.
Assuntos
Compostos Férricos/química , Metais/química , Metais/isolamento & purificação , Amido/química , Aço , Purificação da Água/economia , Água/química , Adsorção , Custos e Análise de Custo , Concentração de Íons de Hidrogênio , Indústrias , Cinética , Nanocompostos/química , Propriedades de Superfície , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
Biocompatible metals have been suggested as revolutionary biomaterials for bone-grafting therapies. Although metals and their alloys are widely and successfully used in producing biomedical implants due to their good mechanical properties and corrosion resistance, they have a lack in bioactivity. Therefore coating of the metal surface with calcium phosphates (CaP) is a benign way to achieve well bioactivity and get controlled corrosion properties. The biocompatibility and bioactivity calcium phosphates (CaP) in bone growth were guided them to biomedical treatment of bone defects and fractures. Many techniques have been used for fabrication of CaP coatings on metal substrates such as magnesium and titanium. The present review will focus on the synthesis of CaP and their relative forms using different techniques especially electrochemical techniques. The latter has always been known of its unique way of optimizing the process parameters that led to a control in the structure and characteristics of the produced materials.