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1.
Molecules ; 29(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38893309

RESUMO

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.8 within 70 min at 40 °C with 5 ng/mL limit of detection for all investigated analytes. It was shown that cyanoacetohydrazide derivatives produces both syn- and anti-forms as well as hydroxylamine, and their ratios were evaluated and shown in presented work. An efficiency enchantment from two to up to five times was achieved with a novel derivatization reagent. Its applicability for qualitative analysis of steroids in urine was presented at real samples. Additionally, the reproducible fragmentation of the derivatizing agent in collision-induced dissociation offers opportunities for simplified non-targeted steroidomic screening. Furthermore, cyanoacetohydrazide increases ionization efficiency in positive mode, which can eliminate the need for redundant high-resolution instrument runs required for both positive and negative mode analyses.


Assuntos
Esteroides , Humanos , Esteroides/urina , Esteroides/química , Cromatografia Líquida de Alta Pressão/métodos , Hidrazinas/química , Espectrometria de Massas em Tandem/métodos , Limite de Detecção
2.
Front Immunol ; 15: 1392992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895128

RESUMO

Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.


Assuntos
Autoanticorpos , Glicoproteína Mielina-Oligodendrócito , Esteroides , Humanos , Masculino , Adulto , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Esteroides/uso terapêutico , Resultado do Tratamento , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite/tratamento farmacológico , Encefalite/imunologia , Encefalite/diagnóstico , Receptores de N-Metil-D-Aspartato/imunologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
4.
Cell Transplant ; 33: 9636897241257568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832653

RESUMO

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.


Assuntos
Anticorpos Monoclonais , Basiliximab , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Proteínas Recombinantes de Fusão , Humanos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Basiliximab/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Estudos Retrospectivos , Adolescente , Irmãos , Adulto Jovem , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Doença Aguda , Criança , Resultado do Tratamento , Doadores de Tecidos
5.
Cancer Lett ; 596: 216998, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830470

RESUMO

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are rare but fatal, requiring systemic steroid use. Therefore, to examine the outcomes, incidence, timing, and risk factors of ICI-associated steroid-requiring severe irAEs, we conducted a nationwide, retrospective, cohort study utilizing the Korean Health Insurance and Review Assessment database. We identified 357,010 patients with lung cancer, bladder cancer, or skin melanoma, eligible for ICI reimbursement in Korea between January 2012 to June 2020. Steroid-requiring severe irAEs following ICI treatment or treatment-emergent AEs following cytotoxic chemotherapy were defined as moderate- or high-dose steroid administration for over 2 consecutive days, along with corresponding ICD-10 codes indicating affected organ systems. The ICI-exposed group (N = 10,118) was compared to a matched cohort of 55,436 ICI-unexposed patients treated with cytotoxic chemotherapy. Incidences of acute severe irAEs requiring moderate- and high-dose steroids were higher in the ICI-exposed group (1.95% and 6.42%, respectively). The ICI-exposed group also had a higher risk of developing delayed severe irAEs requiring moderate- and high-dose steroid use (3.89% and 7.39%). Male sex, high comorbidity index, or previously diagnosed autoimmune diseases were associated with an increased risk of severe irAEs. Notably, 27.4-38.8% of the patients experienced recurrent severe irAEs after re-challenge with ICIs following moderate- or high-dose steroid use, with the severity matching the initial episode. Steroid-requiring severe irAEs were significantly more prevalent among patients exposed to ICIs than among those treated with chemotherapy in acute and delayed periods.


Assuntos
Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Fatores de Risco , Incidência , Pessoa de Meia-Idade , Idoso , República da Coreia/epidemiologia , Melanoma/tratamento farmacológico , Melanoma/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Adulto , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Esteroides/uso terapêutico , Esteroides/administração & dosagem
7.
Clin Neurol Neurosurg ; 242: 108325, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776717

RESUMO

OBJECTIVES: The study aims to retrospectively compare steroid and radiofrequency treatments for the greater occipital nerve(GON) under ultrasound guidance in chronic migraine. METHODS: Monthly average headache attack frequency, attack duration, visual analog scale(VAS) and the number of days analgesics were taken were recorded. Under ultrasound guidance, GON block was administered once a week for a total of four sessions. In the final session, 4 mg of dexamethasone was added to the local anesthetic for the steroid group (n:26). Pulsed radiofrequency (RF) treatment was applied to the RF group (n:25) just before the last session of the GON block. The pain course in the week following the procedure monthly average headache attack frequency, attack duration, VAS and the number of days analgesics were taken in a month were compared for both groups at 1-3-6 months. RESULTS: In the first month, a statistically significant decrease in attack frequency was observed in the RF group. However, no statistically significant differences were found between the groups in other findings at different time intervals. A significant decrease headache attack duration,VAS, and the number of days analgesics were taken in a month was observed in both treatment groups. Both treatments were found to be effective, but the effect size of the treatment was higher in the RF group compared to the steroid group. CONCLUSION: Although the results were better in the group receiving pulsed RF treatment, except for the attack frequency in the first month, no statistically significant superiority of one treatment method over the other was determined.


Assuntos
Dexametasona , Transtornos de Enxaqueca , Bloqueio Nervoso , Humanos , Transtornos de Enxaqueca/terapia , Masculino , Adulto , Bloqueio Nervoso/métodos , Feminino , Pessoa de Meia-Idade , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Doença Crônica , Tratamento por Radiofrequência Pulsada/métodos , Nervos Espinhais/efeitos dos fármacos , Esteroides/administração & dosagem , Esteroides/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-38797241

RESUMO

Crassostrea angulata, a major shellfish cultivated in Southern China, has experienced a notable surge in commercial value in recent years. Understanding the molecular mechanisms governing their reproductive processes holds significant implications for advancing aquaculture practices. In this study, we cloned the orphan nuclear receptor gene, Fushi Tarazu transcription factor 1 (FTZ-F1), of C. angulata and investigated its functional role in the gonadal development. The full-length cDNA of FTZ-F1 spans 2357 bp and encodes a protein sequence of 530 amino acids. Notably, the amino acid sequence of FTZ-F1 in C. angulata shares remarkable similarity with its homologues in other species, particularly in the DNA-binding region (>90%) and ligand-binding region (>44%). In C. angulata, the highest expression level of FTZ-F1 was observed in the ovary, exhibiting more than a 200-fold increase during the maturation stage compared to the initiation stage (P < 0.001). Specifically, FTZ-F1 was mainly expressed in the follicular cells surrounding the oocytes of C. angulata. Upon inhibiting FTZ-F1 gene expression in C. angulata through RNA interference (RNAi), a substantial reduction in the expression of genes involved in the synthesis of sex steroids in the gonads, including 3ß-HSD, Cyp17, and follistatin, was observed. In addition, estradiol (E2) and testosterone (T) levels also showed a decrease upon FTZ-F1 silencing, resulting in a delayed gonadal development. These results indicate that FTZ-F1 acts as a steroidogenic factor, participating in the synthesis and regulation of steroid hormones and thus playing an important role in the reproductive and endocrine systems within oysters.


Assuntos
Crassostrea , Gônadas , Fatores de Transcrição , Animais , Crassostrea/genética , Crassostrea/crescimento & desenvolvimento , Crassostrea/metabolismo , Gônadas/metabolismo , Gônadas/crescimento & desenvolvimento , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Feminino , Sequência de Aminoácidos , Regulação da Expressão Gênica no Desenvolvimento , Filogenia , Clonagem Molecular , Hormônios Esteroides Gonadais/metabolismo , Hormônios Esteroides Gonadais/biossíntese , Ovário/metabolismo , Ovário/crescimento & desenvolvimento , Esteroides/metabolismo , Esteroides/biossíntese
9.
Phytochemistry ; 224: 114140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38750709

RESUMO

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.


Assuntos
Alcaloides , Fritillaria , Raízes de Plantas , Fritillaria/química , Raízes de Plantas/química , Estrutura Molecular , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Cevanas/química , Cevanas/farmacologia , Cevanas/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Animais , Conformação Molecular , Cristalografia por Raios X , Linhagem Celular , Ratos , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Modelos Moleculares
10.
Pain Physician ; 27(4): 229-234, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38805529

RESUMO

BACKGROUND: Transforaminal epidural steroid injection (TFESI) is commonly used for radicular pain, but can lead to an unintentional injection into the retrodural Space of Okada (RSO), an extradural space located dorsal to the ligamentum flavum, instead of the epidural space. OBJECTIVES: To determine the prevalence and describe the fluoroscopic imaging features of an unintentional injection into the RSO during a TFESI and to review the history of injections into the RSO. STUDY DESIGN: Observational study and original research. SETTING: This work was conducted at Jeju National University School of Medicine, Jeju, Republic of Korea. METHODS: A total of 5,429 lumbar TFESIs performed from the September 1, 2018 through October 31, 2021 were analyzed for unintentional RSO injections using fluoroscopic-guided contrast medium patterns. RESULTS: The rate of unintentional injection into the RSO was 0.20% (11 incidents). Contrast medium patterns in the RSO had a sigmoid or ovoid shape confined to the affected facet joint, or a butterfly-shaped pattern extending into the contralateral facet joint, but rarely extending beyond the upper or lower level. LIMITATION: The rarity of unintentional injection into the RSO prevented a randomized controlled study design. CONCLUSIONS: Careful fluoroscopic examination of contrast medium patterns during lumbar TFESI is crucial to identify needle placement in the RSO. If detected, the procedure can be corrected by slightly advancing the needle into the foramen.


Assuntos
Esteroides , Humanos , Injeções Epidurais/métodos , Injeções Epidurais/efeitos adversos , Fluoroscopia , Esteroides/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Ligamento Amarelo , Idoso , República da Coreia , Vértebras Lombares
11.
Eur J Med Chem ; 272: 116460, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704943

RESUMO

It has been reported that 4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazolinone and dihydropyrazole moiety into steroid skeleton to design and synthesize a novel series of D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives, and assessed their in vitro anti-inflammatory profiles against Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. The anti-inflammatory activities assay demonstrated that compound 12e was considered as the most effective anti-inflammatory drug, which suppressed the expression of pro-inflammatory mediators including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), it also dose-dependently inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 macrophage cells. Furthermore, the results of the Western blot analysis showed a correlation between the inhibition of the Nuclear factor-kappa B (NF-κB) and Mitogen-activated protein kinases (MAPKs) signaling pathways and the suppressive effects of compound 12e on pro-inflammatory cytokines. Molecular docking studies of compound 12e into the COX-2 protein receptor (PDB ID: 5IKQ) active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of dexamethasone (DXM), explaining their remarkable COX-2 inhibitory activity. The findings revealed that these candidates could be identified as potent anti-inflammatory agents, compound 12e could be a promising drug for the treatment of inflammatory diseases.


Assuntos
Ciclo-Oxigenase 2 , Regulação para Baixo , Desenho de Fármacos , Lipopolissacarídeos , Macrófagos , NF-kappa B , Óxido Nítrico Sintase Tipo II , Pirazóis , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Células RAW 264.7 , Ciclo-Oxigenase 2/metabolismo , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Relação Estrutura-Atividade , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Estrutura Molecular , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Modelos Moleculares , Relação Dose-Resposta a Droga , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Tiazóis/farmacologia , Tiazóis/química , Tiazóis/síntese química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Esteroides/farmacologia , Esteroides/química , Esteroides/síntese química , Simulação de Acoplamento Molecular
12.
Br J Oral Maxillofac Surg ; 62(5): 448-452, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782637

RESUMO

Maxillofacial trauma often brings significant challenges for surgeons in terms of preoperative oedema. Steroids offer oedema reduction, yet potentially increase the risks of postoperative infection. This study explores procalcitonin (PCT), as a marker for bacterial infection risk, and interleukins IL-6 and IL-10, which respectively signify pro-inflammatory and anti-inflammatory responses, as potential indicators of infection and inflammation in these trauma cases and thereby aid in refining perioperative guidelines for the use of steroids. A prospective study was conducted at a tertiary public hospital in India from 2019 to 2022 on patients >18 years with facial trauma. After specific exclusions, patients were randomised into steroid (Group A) and non-steroid (Group B) groups. Various parameters including oedema, PCT, IL-6, and IL-10 levels were measured and analysed using SPSS software. Out of 80 patients, 44 were in Group A and 36 in Group B. Post-24 hours, Group A showed significant oedema reduction, with 25 patients displaying a decline to mild oedema, versus 10 patients in Group B (p = 0.034). However, Group A witnessed a higher infection risk, with 20 patients showing positive wound cultures versus three in Group B. Subgroup analysis revealed a link between higher PCT levels and infections (p = 0.039). Additionally, Group A showed less intraoperative bleeding and reduced operating time. While perioperative steroids mitigate swelling, they might increase postoperative infection risk. Elevated PCT levels indicate potential wound infections, suggesting those patients should avoid perioperative steroids. IL-6 and IL-10 trends during perioperative phases can predict pronounced oedema outcomes.


Assuntos
Biomarcadores , Interleucina-10 , Interleucina-6 , Traumatismos Maxilofaciais , Pró-Calcitonina , Humanos , Interleucina-6/sangue , Interleucina-10/sangue , Pró-Calcitonina/sangue , Masculino , Estudos Prospectivos , Feminino , Biomarcadores/sangue , Adulto , Traumatismos Maxilofaciais/sangue , Traumatismos Maxilofaciais/cirurgia , Pessoa de Meia-Idade , Edema/etiologia , Infecção da Ferida Cirúrgica/etiologia , Índia , Esteroides/uso terapêutico , Valor Preditivo dos Testes
13.
Biochem Pharmacol ; 225: 116266, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710333

RESUMO

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer.


Assuntos
Antineoplásicos , Compostos de Epóxi , Neoplasias Pulmonares , Neoplasias da Próstata , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Compostos de Epóxi/farmacologia , Compostos de Epóxi/química , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Apoptose/efeitos dos fármacos , Esteroides/farmacologia , Esteroides/química , Relação Dose-Resposta a Droga
14.
J Steroid Biochem Mol Biol ; 242: 106545, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38762058

RESUMO

Most breast and prostate cancers are caused by abnormal production or action of steroidal hormones. Hormonal drugs based on steroid scaffolds represent a significant class of chemotherapeutics that are routinely used in chemotherapy. In this study, the synthesis of new 17a-homo lactone and 17α-(pyridine-2-ylmethyl) androstane derivatives with hydrazide and semicarbazone motifs is presented. All compounds were screened for their effect on cell viability against a panel of five cancer cell lines and one healthy cell line. Two compounds showed significant cytotoxicity against cancer cells, with low toxicity against healthy cells. The relative binding affinities of compounds for the ligand-binding domains of estrogen receptor α, estrogen receptor ß, androgen receptor and glucocorticoid receptor were tested using a fluorescence screen in yeast. Potential for inhibition of aldo-keto reductase 1C3 and 1C4 activity was measured in vitro. Experimental results are analyzed in the context of molecular docking simulations. Our results could help guide design of steroid compounds with improved anticancer properties against androgen- and estrogen-dependent cancers.


Assuntos
Antineoplásicos , Simulação de Acoplamento Molecular , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Hidrazinas/farmacologia , Hidrazinas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Esteroides/química , Esteroides/farmacologia , Semicarbazonas/farmacologia , Semicarbazonas/química , Semicarbazonas/síntese química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/química , Ensaios de Seleção de Medicamentos Antitumorais
15.
Pancreatology ; 24(4): 538-544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38693038

RESUMO

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS: 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) µg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 µg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) µg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.


Assuntos
Pancreatite Autoimune , Insuficiência Pancreática Exócrina , Humanos , Pancreatite Autoimune/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Pancreática Exócrina/tratamento farmacológico , Pâncreas Exócrino/efeitos dos fármacos , Adulto , Esteroides/uso terapêutico , Elastase Pancreática
16.
Am J Otolaryngol ; 45(4): 104359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38729018

RESUMO

PURPOSE: To assess whether preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin E (IgE), and blood eosinophil percentage (EOS) can predict need for steroid irrigations after FESS. MATERIALS AND METHODS: Adult patients at BIDMC from inception until September 8, 2023 with chronic rhinosinusitis with nasal polyps who underwent FESS and had preoperative CRP (n = 129), ESR (n = 79), IgE (n = 107), or EOS (n = 125) were included. Labs were divided into normal (CRP: 0-5.0 mg/L; ESR: 0-15 mm/h; IgE: 150-300Ul/mL; EOS: 1-7 %) and high groups (CRP: >5.0 mg/L; ESR: >15 mm/h; IgE: >300Ul/mL; EOS: >7 %). The primary outcome was need for intranasal steroid irrigations after FESS (≤4 weeks, 4-12 weeks, 12-26 weeks, 26-52 weeks, 1-3 years, 3-5 years, and > 5 years). Receiver operating characteristic curves were created to determine thresholds for predicting postoperative steroid irrigations. RESULTS: Elevated IgE required intranasal steroid irrigation at 1-3 years (normal 34 %, high 62 %, p = 0.02), 3-5 years (normal 24 %, high 48 %, p = 0.04), and > 5 years (normal 19 %, high 43 %, p = 0.02). Elevated EOS required intranasal steroid irrigation at 26-52 weeks (normal 7 %, high 25 %, p = 0.009) and > 5 years (normal 19 %, high 46 %, p = 0.005). The area under the curve for IgE at 1-3 years was 0.696 (95 % CI: 0.597-0.795) with cutoff at 144-148 Ul/mL. CRP and ESR were not predictive of postoperative intranasal steroid treatment. CONCLUSIONS: Elevated IgE and EOS (but not CRP or ESR) may predict need for intranasal steroid treatment after FESS.


Assuntos
Sedimentação Sanguínea , Proteína C-Reativa , Imunoglobulina E , Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/cirurgia , Pólipos Nasais/cirurgia , Pólipos Nasais/sangue , Rinite/cirurgia , Rinite/sangue , Doença Crônica , Masculino , Feminino , Pessoa de Meia-Idade , Imunoglobulina E/sangue , Adulto , Proteína C-Reativa/análise , Eosinófilos , Esteroides/administração & dosagem , Valor Preditivo dos Testes , Lavagem Nasal/métodos , Endoscopia/métodos , Período Pré-Operatório , Cuidados Pré-Operatórios/métodos , Irrigação Terapêutica/métodos , Idoso , Rinossinusite
17.
Int J Biol Macromol ; 269(Pt 1): 132020, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704061

RESUMO

A series of D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one attached to an electron-releasing (ER) or electron-withdrawing (EW) groups via steroidal oxoacetate intermediate were synthesized to investigate their protein aggregation inhibition potential using human lysozyme (HLZ). The influence of the type of substituent at the C-6 positions of the quinoxalin-2(1H)-one ring on the protein aggregation inhibition potential was observed, showing that the EW moiety improved the protein aggregation inhibition potency. Of all the evaluated compounds, NO2-substituted quinoxalin-2(1H)-one derivative 13 was the most active compound and had a maximum protein aggregation inhibition effect. Significant stabilization effects strongly support the binding of the most biologically active steroidal quinoxalin-2(1H)-one with docking studies. The predicted physicochemical and ADME properties lie within a drug-like space which shows no violation of Lipinski's rule of five except compounds 12 and 13. Combined, our results suggest that D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one has the potential to modulate the protein aggregation inhibition effect.


Assuntos
Simulação de Acoplamento Molecular , Muramidase , Agregados Proteicos , Quinoxalinas , Quinoxalinas/química , Quinoxalinas/farmacologia , Agregados Proteicos/efeitos dos fármacos , Humanos , Muramidase/química , Muramidase/metabolismo , Esteroides/química , Esteroides/farmacologia , Dobramento de Proteína
18.
Medicina (Kaunas) ; 60(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38792992

RESUMO

Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain.


Assuntos
Dor Lombar , Esteroides , Humanos , Estudos Retrospectivos , Fluoroscopia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Injeções Epidurais/métodos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Dor Lombar/tratamento farmacológico , Adulto , Idoso , Ultrassonografia de Intervenção/métodos , Resultado do Tratamento , Radiculopatia/tratamento farmacológico , Radiculopatia/complicações , Estudos de Casos e Controles , Vértebras Lombares , Ultrassonografia/métodos , Região Lombossacral
19.
Zool Res ; 45(3): 617-632, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38766745

RESUMO

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.


Assuntos
Glândulas Suprarrenais , Esteroides , Animais , Glândulas Suprarrenais/metabolismo , Humanos , Esteroides/biossíntese , Esteroides/metabolismo , Transcriptoma , Camundongos , Tupaiidae , Feminino , Multiômica
20.
Anal Chim Acta ; 1308: 342658, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38740458

RESUMO

BACKGROUND: The environmental impact of sample preparation should be minimized through simplification of the procedures and the use of natural, renewable and/or reusable materials. In such scenario, thin-film microextraction fulfils the former criteria, as it enables few steps and miniaturization, thus small amount of extraction phase. At the same time, the use of sorbents such as biochars obtained from biomass waste is even more promoted due to their availability at low cost and increased life-cycle in a circular economy vision. However, it is not always easy to combine these criteria in sample preparation. RESULTS: A thin film microextraction was developed for the determination of steroids in aqueous samples, entailing a membrane made of cellulose triacetate and a wood-derived biochar (Nuchar®) as carbon precursor. Different characterization techniques showed the successful preparation, whereas the sorption kinetics experiments demonstrated that biochar is responsible for the extraction with the polymer acting as a smart support. After a study about membranes' composition in terms of biochar amounts (4 %, 10 %, 16 % wt) and type of synthesis set up, the ceramic 3D-mold was selected, achieving reproducible and ready-to-use membranes with composition fixed as 10 %. Different elution conditions, viz. type and time of agitation, type, composition and volume of eluent, were evaluated. The final microextraction followed by HPLC-MS/MS quantification was successfully validated in river and wastewater treatment plant effluent samples in terms of accuracy (R% 64-123 %, RSD<19 % in river; R% 61-118 %, RSD <18 % in effluent, n = 4), sensitivity (MQLs 0.2-8.5 ng L-1) and robustness. SIGNIFICANCE: This novel biochar-based polymeric film proved to be a valid and sustainable sorbent, in terms of extraction capability, ease of preparation and greenness. By comparison with literature and the greenness evaluation with the most recent metric tools, this method expands the potential applicability of the thin-film microextraction and opens up innovative scenarios for sustainable procedures entailing the use of biochars entrapped in bio-polymers.


Assuntos
Carvão Vegetal , Polímeros , Águas Residuárias , Poluentes Químicos da Água , Carvão Vegetal/química , Águas Residuárias/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Polímeros/química , Adsorção , Esteroides/análise , Esteroides/química , Esteroides/isolamento & purificação , Microextração em Fase Sólida/métodos
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