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1.
Med Chem ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38192145

RESUMO

BACKGROUND: The elucidation of molecular pathways associated with adipogenesis has evidenced the relevance of estrogen and estrogen receptor beta (ERß). The positive effects of ERß ligands on adipogenesis, energy expenditure, lipolysis, food intake, and weight loss, make ERß an attractive target for obesity control. From ligand-based virtual screening, molecular docking, and molecular dynamic simulations, six new likely ERß ligands (C1 to C6) have been reported with potential for pharmacological obesity treatment. OBJECTIVE: In this study, the effect of molecules C1-C6 on adipogenesis using the murine 3T3-L1 cell line was evaluated. METHODS: Cell viability was assessed by MTT assays. Lipid accumulation and gene expression were investigated by ORO staining and real-time quantitative RT-PCR experiments, respectively. RESULTS: Cell viability was not significantly affected by C1-C6 at concentrations up to 10 µM. Interestingly, treatment with 10 µM of C1 (S-Dihydrodaidzein) and C2 (3-(1,3-benzoxazol-2-yl)- benzamide) for 72 h inhibited adipocyte differentiation; moreover, ORO staining evidenced a reduced intracellular lipid accumulation (40% at day 7). Consistently, mRNA expression of the adipogenic markers, PPARγ and C/EBPα, was reduced by 50% and 82%, respectively, in the case of C1, and by 83% and 59%, in the case of C2. CONCLUSION: Altogether, these results show the two new potential ß-estrogen receptor ligands, C1 and C2, to exhibit anti-adipogenic activity. They could further be used as lead structures for the development of more efficient drugs for obesity control.

2.
Case Rep Oncol Med ; 2024: 5093727, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264474

RESUMO

Peritoneal cancer is the invasion by malignant cells of serous membrane that lines the abdominal cavity, the viscera, and the coelom of the amniotes. Histologically, it is indistinguishable from ovarian counterpart, although in the former, it commonly involves the ovary only superficially, or it may totally lack an ovarian component, but with extensive involvement of the peritoneum, calcified perihepatic peritoneal nodules, or involvement of the omentum, in most cases. The current study describes the case of a 54-year-old female patient referring a history of colitis and dairy intolerance. A transvaginal ultrasound and a computed tomography (CT) scan revealed a tumor measuring 70 × 61 × 63 mm. CA-125 serum levels were 880 U/ml. Laparotomy surgery was indicated, and tumor was found at the level of the rectovaginal septum without evidence of metastasis. Tumor dissection and protective colostomy with loop sigmoid colon were performed. A pathological study gave a diagnosis of a high-grade peritoneal serous carcinoma with a micropapillary pattern. The present study describes the case of papillary serous peritoneal cancer presented as a single tumor mass without extensive involvement of the peritoneum. Additionally, the need for routine tests for its diagnosis and documenting hormonal alterations as the cause of its origin are suggested.

3.
Otol Neurotol ; 44(10): e697-e701, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37733986

RESUMO

OBJECTIVES: The purpose of this study is to evaluate the reliability of temporal bone density measurements for diagnosing otosclerosis. MATERIALS AND METHODS: A retrospective case-control study is presented. Bone density was measured in Hounsfield units (HUs) by using high-resolution computed tomography in eight regions of interest (ROI) where otosclerotic foci are usually localized. The density of 113 otosclerotic ears was compared with that of 33 nonotosclerotic ears to determine sensitivity and specificity. Furthermore, the binormal receiver operating characteristic curve of each ROI's density was calculated to estimate the diagnostic value for osteosclerosis. In addition, the radiological density of seven cases-where radiological visual examination exhibited no findings but surgery confirmed stapes fixation-was compared with nonotosclerotic controls. RESULTS: ROI densities were significantly lower in otosclerotic patients compared with nonotosclerotic controls. The area under the curve of the fissula ante fenestram (FAF) presented the highest diagnostic performance: 1,871 HU cut-off value (area under the curve = 0.986), 96.64% sensitivity, and 100% specificity. Significantly lower densities in the FAF area were observed in the seven cases with negative radiology but intraoperatively confirmed otosclerosis. CONCLUSION: The high-resolution computed tomography density of the FAF is a reliable measurement for diagnosing otosclerosis. A value less than 1,871 HU exhibited the highest sensitivity and specificity in a European Caucasian population.


Assuntos
Otosclerose , Humanos , Otosclerose/diagnóstico por imagem , Otosclerose/cirurgia , Estudos Retrospectivos , Estudos de Casos e Controles , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Densitometria
4.
Pharmaceuticals (Basel) ; 16(7)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37513861

RESUMO

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

5.
Bioorg Chem ; 138: 106624, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295238

RESUMO

Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.


Assuntos
Antiprotozoários , Leishmaniose , Compostos de Selênio , Animais , Camundongos , Antiprotozoários/química , Macrófagos , Leishmaniose/tratamento farmacológico , Compostos de Selênio/farmacologia , Camundongos Endogâmicos BALB C
7.
Antioxidants (Basel) ; 12(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36671001

RESUMO

Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer's disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound 13a showed concentration- and time-dependent radical scavenging activity. Additionally, compounds 14a and 17a showed high activity in the melanoma and ovarian cancer cell lines, with LD50 values below 9.2 µM. Interestingly, in the AChEI test, compound 14a showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10-6 cm/s). Molecular dynamics simulations of the aspirin derivatives (14a and 14b) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as 14a, might become very promising candidates to treat both cancer and AD.

8.
Orbit ; 42(1): 104-106, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34470541

RESUMO

Proliferative fasciitis (PF) is a benign fibroblastic reaction with histological and clinical characteristics that overlap with those of malignant soft tissue tumors; thus, it is referred to as a pseudosarcomatous reaction. It continues to be an important cause of diagnostic error and overtreatment. The childhood PF subtype has some distinct histological and immunohistochemical characteristics that make differential diagnosis with malignant tumors even harder, especially with sarcoma. These proliferations generally occur in the lower limbs, and the periorbital region is a rare location of appearance. Here, we describe a case of childhood subtype PF in a 16-year-old girl located in the periorbital area. To the best of our knowledge, this is the first reported case of childhood subtype PF in the periorbital area, and the third case if PF subtypes are not taken into account.


Assuntos
Fasciite , Neoplasias Orbitárias , Sarcoma , Neoplasias de Tecidos Moles , Feminino , Humanos , Adolescente , Órbita/patologia , Fasciite/diagnóstico , Fasciite/patologia , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/patologia , Face/patologia , Diagnóstico Diferencial , Neoplasias Orbitárias/diagnóstico por imagem
9.
Food Technol Biotechnol ; 61(4): 536-548, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38205055

RESUMO

Research background: Soursop nectar contains antioxidants and is preserved by pasteurization. However, this technology impairs its physicochemical properties and bioactive compounds. An alternative is therefore thermoultrasound, which could counteract these effects. The thermosonicated nectar was compared with a pasteurized one and the in vitro bioaccessibility of antioxidants was estimated. Experimental approach: The soursop nectar (25 %) was processed and the response surface methodology was used to determine the optimal conditions for thermoultrasound treatment (TUS). The TUS (75-90 % amplitude, 3.15-15 min) was applied, and 2 % stevia and 6 % agave inulin were added as sweeteners. The microbiological, physicochemical, enzymatic and antioxidant properties were analyzed. The properties of thermosonicated nectar obtained under optimal conditions were compared with pasteurized nectar. In addition to the above determinations, microstructure, total dietary fiber (TDF) and in vitro bioaccessibility of antioxidants were determined. Results and conclusions: The response variables that fit the mathematical model were L*, b*, chroma (C*), total phenolic content (TPC) and antioxidant activity determined by ABTS•+, DPPH˙ and Fe(III) reducing antioxidant power (FRAP). The L* and DPPH˙ were affected by quadratic time and TPC by time (p<0.0001). The optimum TUS condition was 82 % amplitude for 9.15 min and the responses variables were L*, b* and C* (45.48, 3.55 and 3.62, respectively), TPC expressed as gallic acid equivalents (38.40 mg/100 mL), ABTS•+ expressed as Trolox equivalents (TE) (31.28 µmol/100 mL), DPPH˙ expressed as TE (124.22 µmol/100 mL) and FRAP expressed as Fe(II) (3.06 µmol/100 mL). Compared to the pasteurized sample, thermosonicated sample had high values of L* (45.56), h° (-56.49), TPC (26.63 mg/100 mL), ABTS•+ and DPPH˙ (22.03 and 129.22 µmol/100 mL, respectively), FRAP (3.10 µmol/100 mL) and low pectin methylesterase (PME) activity (0.28 U/mL). For in vitro bioaccessibility, thermosonicated nectar showed high absorption of TPC (15.26/100 mL) and high antioxidant activity determined by ABTS (34.92 µmol/100 mL) and FRAP (7.88 µmol/100 mL). Novelty and scientific contribution: The thermoultrasound improves the physicochemical properties and in vitro bioaccessibility of antioxidants in soursop nectar. On the other hand, as an alternative, this beverage offers low-calorie alternative with prebiotic properties that benefits consumer health.

10.
Pharmaceuticals (Basel) ; 15(12)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36558915

RESUMO

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed.

11.
Pharmaceutics ; 14(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36432719

RESUMO

The lack of safe and cost-effective treatments against leishmaniasis highlights the urgent need to develop improved leishmanicidal agents. Antimicrobial peptides (AMPs) are an emerging category of therapeutics exerting a wide range of biological activities such as anti-bacterial, anti-fungal, anti-parasitic and anti-tumoral. In the present study, the approach of repurposing AMPs as antileishmanial drugs was applied. The leishmanicidal activity of two synthetic anti-lipopolysaccharide peptides (SALPs), so-called 19-2.5 and 19-4LF was characterized in Leishmania major. In vitro, both peptides were highly active against intracellular Leishmania major in mouse macrophages without exerting toxicity in host cells. Then, q-PCR-based gene profiling, revealed that this activity was related to the downregulation of several genes involved in drug resistance (yip1), virulence (gp63) and parasite proliferation (Cyclin 1 and Cyclin 6). Importantly, the treatment of BALB/c mice with any of the two AMPs caused a significant reduction in L. major infective burden. This effect was associated with an increase in Th1 cytokine levels (IL-12p35, TNF-α, and iNOS) in the skin lesion and spleen of the L. major infected mice while the Th2-associated genes were downregulated (IL-4 and IL-6). Lastly, we investigated the effect of both peptides in the gene expression profile of the P2X7 purinergic receptor, which has been reported as a therapeutic target in several diseases. The results showed significant repression of P2X7R by both peptides in the skin lesion of L. major infected mice to an extent comparable to that of a common anti-leishmanial drug, Paromomycin. Our in vitro and in vivo studies suggest that the synthetic AMPs 19-2.5 and 19-4LF are promising candidates for leishmaniasis treatment and present P2X7R as a potential therapeutic target in cutaneous leishmaniasis (CL).

12.
Molecules ; 27(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364304

RESUMO

Currently, cancer, leishmaniasis and bacterial infections represent a serious public health burden worldwide. Six cinnamyl and benzodioxyl derivatives incorporating selenium (Se) as selenocyanate, diselenide, or selenide were designed and synthesized through a nucleophilic substitution and/or a reduction using hydrides. Ferrocene was also incorporated by a Friedel-Crafts acylation. All the compounds were screened in vitro for their antiproliferative, antileishmanial, and antibacterial properties. Their capacity to scavenge free radicals was also assessed as a first approach to test their antioxidant activity. Benzodioxyl derivatives 2a-b showed cytotoxicity against colon (HT-29) and lung (H1299) cancer cell lines, with IC50 values below 12 µM, and were also fairly selective when tested in nonmalignant cells. Selenocyanate compounds 1-2a displayed potent antileishmanial activity in L. major and L. infantum, with IC50 values below 5 µM. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 µg/mL. Ferrocene-containing selenide 2c was also identified as a potent antileishmanial agent with radical scavenging activity. Remarkably, derivative 2a with a selenocyanate moiety was found to act as a multitarget compound with antiproliferative, leishmanicidal, and antibacterial activities. Thus, the current work showed that 2a could be an appealing scaffold to design potential therapeutic drugs for multiple pathologies.


Assuntos
Antiprotozoários , Neoplasias , Humanos , Metalocenos , Antiprotozoários/farmacologia , Antibacterianos/farmacologia
13.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077439

RESUMO

Trypanosoma cruzi (T. cruzi) is a parasite that affects humans and other mammals. T. cruzi depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs. In this study, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole as a scaffold was accomplished. Later, a molecular docking on the interface of T. cruzi TIM (TcTIM) was performed and the compounds were grouped by interaction profiles. Subsequently, a selection of compounds was made based on cost and availability for in vitro evaluation against blood trypomastigotes. Finally, the compounds were analyzed by molecular dynamics simulation, and physicochemical and pharmacokinetic properties were determined using SwissADME software. A total of 1604 molecules were obtained as potential TcTIM inhibitors. BP2 and BP5 showed trypanocidal activity with half-maximal lytic concentration (LC50) values of 155.86 and 226.30 µM, respectively. Molecular docking and molecular dynamics simulation analyzes showed a favorable docking score of BP5 compound on TcTIM. Additionally, BP5 showed a low docking score (-5.9 Kcal/mol) on human TIM compared to the control ligand (-7.2 Kcal/mol). Both compounds BP2 and BP5 showed good physicochemical and pharmacokinetic properties as new anti-T. cruzi agents.


Assuntos
Tripanossomicidas , Trypanosoma cruzi , Animais , Benzimidazóis/química , Benzimidazóis/farmacologia , Humanos , Ligantes , Mamíferos/metabolismo , Simulação de Acoplamento Molecular , Triose-Fosfato Isomerase/metabolismo , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/metabolismo
14.
Foods ; 11(9)2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35563955

RESUMO

Obesity is a disease characterized by an inflammatory process in the adipose tissue due to diverse infiltrated immune cells, an increased secretion of proinflammatory molecules, and a decreased secretion of anti-inflammatory molecules. On the other hand, obesity increases the risk of several diseases, such as cardiovascular diseases, diabetes, and cancer. Their treatment is based on nutritional and pharmacological strategies. However, natural products are currently implemented as complementary and alternative medicine (CAM). Polyphenols and fiber are naturally compounds with potential action to reduce inflammation through several pathways and play an important role in the prevention and treatment of obesity, as well as in other non-communicable diseases. Hence, this review focuses on the recent evidence of the molecular mechanisms of polyphenols and dietary fiber, from Scopus, Science Direct, and PubMed, among others, by using key words and based on recent in vitro and in vivo studies.

15.
J Clin Pathol ; 75(6): 383-389, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33722841

RESUMO

BACKGROUND: Secondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH. AIM: Our objective is to ascertain the existence of sHLH in some patients with severe COVID-19. METHODS: We report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records. RESULTS: Eleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case. CONCLUSIONS: Our results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.


Assuntos
COVID-19 , Linfo-Histiocitose Hemofagocítica , Autopsia , Medula Óssea/patologia , COVID-19/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/patologia , Insuficiência de Múltiplos Órgãos/patologia
16.
Nanoscale ; 13(41): 17486-17503, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34651151

RESUMO

This study investigates if visceral leishmaniasis (VL) infection has some effects on the organ and cellular uptake and distribution of 100-200 nm near-infrared fluorescently labelled non-biodegradable polystyrene latex beads (PS NPs) or biodegradable polylactic-co-glycolic nanoparticles (PLGA NPs), as this parasitic infection produces morphological alterations in liver, spleen and bone marrow, organs highly involved in NP sequestration. The results showed that the magnitude of the effect was specific for each organ and type of NP. With the exception of the liver, the general trend was a decrease in NP organ and cellular uptake, mostly due to immune cell mobilization and/or weight organ gain, as vascular permeability was increased. Moreover, NPs redistributed among different phagocytic cells to adapt infection associated changes and cellular alterations. In the liver, it is noteworthy that only isolated Kuffer cells (KCs) captured NPs, whereas they were not taken up by KC forming granulomas. In the spleen, NPs redistributed from macrophages and dendritic cells towards B cells and inflammatory monocytes although they maintained their preferential accumulation in the marginal zone and red pulp. Comparatively, the infection rarely affected the NP cellular distribution in the bone marrow. NP cellular target changes in VL infection could affect their therapeutic efficacy and should be considered for more efficient drug delivery.


Assuntos
Nanopartículas , Doenças Parasitárias , Transporte Biológico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Monócitos
17.
Foods ; 10(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199351

RESUMO

Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota-intestine-brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health-disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.

18.
Int J Clin Pharm ; 43(4): 1123-1127, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33937971

RESUMO

Background Platinum-based therapy continues to be one of the pillars of the treatment of different types of cancer. However, many times the responsible clinician renounces its use after the appearance of a hypersensitivity reaction. Objective To assess the value of skin tests (ST) in clinical practice to address the treatment of patients with suspicion of immediate hypersensitivity reactions (HSRs) to platinum compounds. Method Single-center retrospective study of 3 years. Adult patients treated with any platinum compound who experienced HSR symptoms and for whom an oncologist requested ST, were included. ST with cisplatin, carboplatin and oxaliplatin were performed. Results Twenty-two patients were included. ST were positive in 12 patients (54.5%), of which 4 (33%) presented cross-reactivity to another platinum compound. Fifteen patients continued platinum-based chemotherapy: 9 patients with positive ST (4 continued by desensitization and 5 with another platinum compound) and 6 patients with negative ST, of which 1 repeated an HSR. A NPV of 0.91 was calculated. Conclusion ST helped physicians identify patients most susceptible to platinum derivative allergies and resume platinum-based therapy in many patients for whom no suitable therapeutic alternative was clinically acceptable.


Assuntos
Antineoplásicos , Hipersensibilidade a Drogas , Adulto , Antineoplásicos/efeitos adversos , Carboplatina , Hipersensibilidade a Drogas/diagnóstico , Humanos , Compostos de Platina , Estudos Retrospectivos , Testes Cutâneos
19.
Antioxidants (Basel) ; 10(4)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920484

RESUMO

Breast cancer is a multifactor disease, and many drug combination therapies are applied for its treatment. Selenium derivatives represent a promising potential anti-breast cancer treatment. This study reports the cytotoxic activity of forty-one amides and phosphoramidates containing selenium against five cancer cell lines (MCF-7, CCRF-CEM, HT-29, HTB-54 and PC-3) and two nonmalignant cell lines (184B5 and BEAS-2B). MCF-7 cells were the most sensitive and the selenoamides I.1f and I.2f and the selenium phosphoramidate II.2d, with GI50 values ranging from 0.08 to 0.93 µM, were chosen for further studies. Additionally, radical scavenging activity for all the compounds was determined using DPPH and ABTS colorimetric assays. Phosphoramidates turned out to be inactive as radical scavengers. No correlation was observed for the antioxidant activity and the cytotoxic effect, except for compounds I.1e and I.2f, which showed dual antioxidant and antitumor activity. The type of programmed cell death and cell cycle arrest were determined, and the results provided evidence that I.1f and I.2f induced cell death via autophagy, while the derivative II.2d provoked apoptosis. In addition, Western blot analysis corroborated these mechanisms with an increase in Beclin1 and LC3-IIB and reduced SQSTM1/p62 levels for I.1f and I.2f, as well as an increase in BAX, p21 and p53 accompanied by a decrease in BCL-2 levels for derivative II.2d.

20.
J Craniofac Surg ; 32(4): 1521-1525, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33170828

RESUMO

OBJECTIVE: The aim of the authors' study is to show their surgical results in orbital decompression using different endonasal endoscopic techniques. These approaches are according to the degree of proptosis and the presence or not of sight threatening. METHODS: The authors performed 31 orbital decompressions on 20 Graves orbitopathy patients. Average age at surgery was 52 years. There were 5 males and 15 females. Five patients were diagnosed as having severe or for sight-threatening Graves orbitopathy. These included 3 men and 2 women having an average age of 54 years old. Minimum postsurgical follow-up was 12 months in all patients. RESULTS: Orbital decompression was performed in 15 patients for proptosis and in 5 patients for urgent sight threat. Thirteen orbits showed mild proptosis and 18 orbits presented moderate proptosis. In patients without sight threatening reduction of proptosis had a mean value of 2.8 mm as determined by exophtalmometry, being 3.3 mm when measured on magnetic resonance imaging. The mean millimeter in mild proptosis was between 1.5 and 1.7 and between 3.4 and 4.2 in moderate proptosis. In patients having sight threat mean visual acuity after surgery improved from 0.6 to 0.9.Only 1 patient without diplopia preoperative developed diplopia after surgery (17%). In 55% of patients strabismus and/or eyelid surgery were required.In postoperative follow-up, 2 patients developed a mucocele and 1 patient developed corneal erosion. CONCLUSION: The authors recommend the preservation of the periorbital sling and the anterior ethmoido-maxillary angle in patients with mild-moderate exophthalmos and without threatened vision. In case of sight threatening the authors resected the most periorbita as much as possible.Evidence-based medicine Level V.


Assuntos
Exoftalmia , Oftalmopatia de Graves , Descompressão Cirúrgica , Endoscopia , Exoftalmia/etiologia , Exoftalmia/cirurgia , Feminino , Oftalmopatia de Graves/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Órbita/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
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