RESUMO
Some inflammatory conditions, such as pyoderma gangrenosum, and tumoral conditions, such as lymphoma, may appear as soft tissue infections. Herein, a cutaneous lymphoma patient who was hospitalized with a diagnosis of soft tissue infection and was considered to have pyoderma gangrenosum during follow-up is presented. Immediate histopathological examination should be recommended to diagnose skin soft tissue lesions, especially long-term and unresponsive to treatment.
RESUMO
OBJECTIVE: To investigate the effect of embolic protection device (EPD) use on periprocedural complications in patients with carotid artery stenosis with anatomical variations. METHOD: The study retrospectively evaluated 185 patients who consecutively underwent carotid artery stenting between November 2020 and December 2023. Forty-four patients with difficult anatomical structures, anatomical variations in the common carotid artery (CCA) and internal carotid artery (ICA) (tortuosity, kinking, or coiling), and a CCA-ICA angle of >60 degrees were included in the sample. The patients were divided into two groups according to the use of EPD filters during the procedure and compared in terms of periprocedural events. RESULTS: Of the 44 patients included in the study, 24 (54.5 %) were male, and the mean age of all patients was 68.7 ± 8.7 years. Comorbidities were present in 93.2 % (n = 41) of the patients. The most common comorbidity was hypertension (n = 32, 72.8 %). The CCA-ICA angle was ≥60 degrees in 45.4 % (n = 20) of all patients. ICA tortuosity was detected in 27.2 % (n = 12) of the patients, ICA kinking in 13.6 % (n = 6), ICA coiling in 6.8 % (n = 3), and CCA tortuosity in 6.8 % (n = 3). Procedure-related periprocedural events developed in 38.6 % (n = 17) of the patients. Postprocedural mortality occurred in two patients, secondary to myocardial infarction in one and COVID-19 pneumonia in the other. There was no significant difference between the filter and non-filter groups in relation to periprocedural events (p = 0.638). Major stroke did not occur in either group. Minor neurological events occurred in 15 % (n = 3/20) of the patients in the filter group and 16.7 % (n = 4/24) of those in the non-filter group. The incidence of vasospasm was statistically higher in patients using filters compared to those without filters (30 % vs. 0 %; P = 0.005, respectively). CONCLUSION: Evaluation of vascular anatomy before carotid artery stenting is important to decide on the technical procedure to be applied in the procedure. The use of EPD in unfavorable anatomy does not reduce periprocedural neurological events. Instead, it results in technical difficulties, prolongs the duration of procedure, and leads to arterial vasospasm. Considering the high periprocedural events in this study, carotid endarterectomy may be a better alternative to endovascular treatment in patients with unfavorable carotid artery anatomy.
RESUMO
In pursuit of identifying small molecule inhibitors of acetylcholinesterase (AChE), the synthesis of new 2-pyrazolines was performed efficiently. A modified spectrophotometric method was used to examine their inhibitory effects on AChE as well as butyrylcholinesterase. Four compounds (2a, 2g, 2j, and 2l) were identified as selective AChE inhibitors. Molecular docking studies were conducted to explore their potential interactions with the active site of AChE (PDB code: 4EY7). 1-(3-Nitrophenyl)-3-(thiophen-3-yl)-5-[4-(4-morpholinyl)phenyl]-2-pyrazoline (2l) exerted significant AChE inhibitory action with an IC50 value of 0.040 µM close to donepezil (IC50 = 0.021 µM). In addition to π-π interactions with Tyr341, Tyr124, and Trp86 residues, compound 2l was also capable of forming two hydrogen bonds and a salt bridge at the active site of AChE thanks to its nitro group at the meta position of the phenyl moiety linked to the N 1 position of the pyrazoline scaffold. The higher inhibitory effect of compound 2l on AChE when compared to other compounds in this series might be explained by these additional interactions. Based on the in vitro parallel artificial membrane permeability assay, compound 2l was found to have high blood-brain barrier permeability. In vitro and in silico studies suggest that compound 2l is a potent inhibitor of AChE, which is an important target for neurodegenerative disorders, particularly Alzheimer's disease.
RESUMO
In search of small molecules for targeted therapy of non-small cell lung carcinoma (NSCLC), an efficient four-step synthetic route was followed for the synthesis of new imidazothiazole-hydrazone hybrids, which were assessed for their cytotoxic effects on human lung adenocarcinoma (A549) and human lung fibroblast (CCD-19Lu) cells. Among them, compounds 4, 6, 13, 16, 17 and 21 exhibited selective cytotoxic activity against A549 cell line. In vitro mechanistic studies were performed to assess their effects on apoptosis, caspase-3, cell cycle, EGFR and Akt in A549 cells. Compounds 6, 16, 17 and 21 promoted apoptotic cell death more than erlotinib. According to the in vitro data, it is quite clear that compound 6 promotes apoptosis through caspase-3 activation and arrests the cell cycle at the G0/G1 phase in A549 cells. Compounds 16 and 17 arrested the cell cycle at the S phase, whereas compounds 4, 13 and 21 caused the cell cycle arrest at the G2/M phase. The most effective EGFR inhibitor in this series was found as compound 13, followed by compounds 17 and 16. Furthermore, Akt inhibitory effects of compounds 16 and 17 in A549 cells were close to that of GSK690693. In particular, it can be concluded that the cytotoxic and apoptotic effects of compounds 16 and 17 are associated with their inhibitory effects on both EGFR and Akt. Molecular docking studies suggest that compounds 16 and 17 interact with crucial amino acid residues in the binding sites of human EGFR (PDB ID: 1M17) and Akt2 (PDB ID: 3D0E). Based on the in silico data, both compounds are predicted to possess favorable oral bioavailability and drug-likeness. Further studies are required to benefit from these compounds as anticancer agents for targeted therapy of NSCLC.
Assuntos
Antineoplásicos , Apoptose , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Hidrazonas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Hidrazonas/farmacologia , Hidrazonas/química , Hidrazonas/síntese química , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Imidazóis/farmacologia , Imidazóis/química , Imidazóis/síntese química , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga , Ciclo Celular/efeitos dos fármacosRESUMO
AIM: To compare the results of fluoroscopically guided transforaminal epidural steroid injection (TESI) for pain reduction in ipsilateral early recurrent lumbar disc herniation (RLDH) with ipsilateral late RLDH. MATERIAL AND METHODS: A total of 738 patients complaining of radicular pain due to ipsilateral early and late RLDH were assessed. Of these, TESI was administered to 390 subjects for ipsilateral early RLDH and 346 for ipsilateral late RLDH. TESIs were performed based on radicular leg pain; all subjects were followed up and reexamined after 12 weeks of the therapy. Pre- and postprocedural visual analog scale (VAS) scores and all complications were recorded for the study. RESULTS: For radicular pain, the mean pre-, and postprocedural VAS scores for ipsilateral early RLDH were 85.44 ± 6.85 and 20.16 ± 3.77 respectively. For late RLDH, the mean pre-, and postprocedural VAS scores were 72.82 ± 5.12 and 30.87 ± 4.17, respectively. A significant statistical difference for pre- and postprocedural VAS scores were observed between ipsilateral early and late recurrent disc herniation TESI groups (p < 0.05). CONCLUSION: TESI was more effective for early RLDH than for late RLDH during the 12-week follow-up period.
Assuntos
Deslocamento do Disco Intervertebral , Vértebras Lombares , Recidiva , Humanos , Deslocamento do Disco Intervertebral/tratamento farmacológico , Masculino , Feminino , Injeções Epidurais/métodos , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Esteroides/administração & dosagem , Medição da Dor , Idoso , FluoroscopiaRESUMO
OBJECTIVES: Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). METHODS: Brain MRI studies of 83 term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) fourth and sixth days were retrospectively re-evaluated by 2 radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major, and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. RESULTS: With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (P = .02 and P = .03, respectively) and ADCmin (P = .03 and P = .04, respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (P = .04) and normal development (P = .04) via cytotoxic oedema of the thalamus, corpus striatum, and diffuse cerebral cortical. CONCLUSION: The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimated similarly with volumetric ADC-HA and the conventional assessment of the ADC map. ADVANCES IN KNOWLEDGE: This study compares early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We could not find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.
Assuntos
Asfixia Neonatal , Imagem de Difusão por Ressonância Magnética , Hipotermia Induzida , Humanos , Recém-Nascido , Hipotermia Induzida/métodos , Asfixia Neonatal/diagnóstico por imagem , Asfixia Neonatal/terapia , Masculino , Feminino , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , PrognósticoRESUMO
BACKGROUND: Seeking health information online has drastically increased. Isotretinoin is one of the agents used to treat acne. OBJECTIVES: In this study, we aimed to investigate the reliability and quality of YouTube videos related to acne treatment, which have been misconception to increase suicide. METHODS: We used the terms "isotretinoin suicide" and "acne treatment suicide" to search YouTube videos. Videos that were not in English, irrelevant, or devoid of audio were not included. The information in the videos was primarily categorized as reliable or unreliable based on its scientific validation. DISCERN and the Global Quality Score were used to evaluate the videos' overall quality. RESULTS: 200 videos in total were examined. 112 videos were included in the study. 39 videos (34.8 %) were found to be reliable, and 73 videos (65.2%) were found to be unreliable. DISCERN values of videos uploaded by physicians or professional organizations and health information websites were found to be significantly higher. There was a statistically significant negative correlation between DISCERN score and video length and the length of time the video was on YOUTUBE, while a positive correlation was observed between DISCERN score and subscriber. CONCLUSION: Although videos created by dermatologists have become widespread in recent years, it is still insufficient. Patient experience videos mostly contain information which does not reflect the reality and emphasize that isotretinoin increases the risk of suicide without evidence. As the number of dermatologists posting videos on YouTube increases, the chances of people accessing correct information will increase.
RESUMO
Merkel cell carcinoma (MCC) is an unusual skin tumor that has a significant rate of distant and local metastases. It is known that primary MCC of the eyelid usually occurs at the upper eyelid. Here we report an unusual case of MCC metastasis to the eyelid. A 63-year-old male was diagnosed with MCC three years earlier after initially presenting with a mass in his right thigh. After histopathological diagnosis, the patient received medical therapy. During treatment, he developed multiple distant metastases and a firm, purple, vascularized lesion on the upper eyelid. We confirmed the lesion was an eyelid metastasis of MCC by histopathological examination and imaging methods. This case shows that extraocular MCC can metastasize to the eyelids, particularly the upper eyelid, where primary periocular MCC usually appears.
Assuntos
Carcinoma de Célula de Merkel , Neoplasias Palpebrais , Neoplasias Cutâneas , Humanos , Masculino , Carcinoma de Célula de Merkel/secundário , Carcinoma de Célula de Merkel/diagnóstico , Pessoa de Meia-Idade , Neoplasias Palpebrais/secundário , Neoplasias Palpebrais/diagnóstico , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Biópsia , Pálpebras/patologiaRESUMO
BACKGROUND: In discharge phase process, supporting patients to develop their own self-care strategies will increase their self-management skills and reduce complications and other health problems that may arise. AIM: The aim of the study is to examine the learning needs of individuals with burns regarding pre-discharge care and treatment and the factors affecting them. METHOD: Data from this cross-sectional study was collected with the "Descriptive Characteristics Form" and "Patient Learning Needs Scale (PLNS)". The study population consisted of patients hospitalized in the adult burn unit of a university hospital in eastern Turkey between May and October 2021. RESULTS: In the present study, it was observed that the pre-discharge learning needs of the patients were at a high level according to the mean score of the general score of the PLNS. Education level, marital status, companion experience and body mass index effected PLNS. CONCLUSIONS: In light of the results, it is recommended that discharge training be planned individually and determined according to the individual's learning needs and affecting factors.
Assuntos
Queimaduras , Alta do Paciente , Humanos , Estudos Transversais , Feminino , Masculino , Queimaduras/terapia , Queimaduras/psicologia , Adulto , Turquia , Alta do Paciente/estatística & dados numéricos , Alta do Paciente/normas , Pessoa de Meia-Idade , Inquéritos e Questionários , Idoso , Avaliação das Necessidades/estatística & dados numéricosRESUMO
Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.
RESUMO
To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions. Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: ⢠COVID-19 in infants and older children has been seen more mildly than in adults. ⢠The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: ⢠Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. ⢠Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.
Assuntos
COVID-19 , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doença Crônica , Tosse/etiologia , COVID-19/epidemiologia , COVID-19/complicações , Estudos Transversais , Turquia/epidemiologiaRESUMO
BACKGROUND: This study was designed to examine the effect of guided imagery applied to geriatric orthopaedic patients on preoperative anxiety and comfort. METHODS: This study was conducted as a randomized controlled trial. The population of the study consisted of geriatric patients treated in the orthopaedics and traumatology clinic of a university hospital. The sample consisted of 80 patients, including the experimental group (n = 40) and the control group (n = 40). Personal Descriptive Form, The State-Trait Anxiety Inventory (STAI) and General Comfort Scale were used as data collection tools. RESULTS: After the guided imagery application, it was determined that the anxiety of the experimental group decreased statistically significantly, and their comfort improved (P < 0.05). CONCLUSION: After the imagery, it was determined that the patients in the experimental group had a decrease in their anxiety level and an improvement in their comfort. Since it is a low-cost and easily accessible method, applying imagery in the preoperative period is recommended.
Assuntos
Imagens, Psicoterapia , Ortopedia , Humanos , Idoso , Imagens, Psicoterapia/métodos , Ansiedade/prevenção & controle , Transtornos de Ansiedade , Período Pré-OperatórioRESUMO
In an attempt to identify small molecules for the treatment of leukemia, 12 new pyrazolines (2a-l) were synthesized efficiently. WST-1 assay was performed to examine their cytotoxic features on HL-60 human acute promyelocytic leukemia (APL), K562 human chronic myeloid leukemia (CML), and THP-1 human acute monocytic leukemia cells. Four compounds (2e, 2f, 2g, and 2h) were determined as promising antileukemic agents on HL-60 and K562 cells. IC50 values of compounds 2f, 2h, 2e, 2g, and bortezomib for the HL-60 cell line were found as 33.52, 42.89, 48.02, 62.34, and 31.75 µM, while IC50 values of compounds 2h, 2g, 2f, 2e, and bortezomib for K562 cells were determined as 33.61, 50.23, 57.28, 76.90, and 42.69 µM, respectively. Further studies were carried out to shed light on the mechanism of antileukemic action. According to the data obtained by in vitro experiments, 1-(4-fluorophenyl)-3-(thiophen-3-yl)-5-(4-(4-methylpiperazin-1-yl)phenyl)-2-pyrazoline (2f) and 1-(3-bromophenyl)-3-(thiophen-3-yl)-5-(4-(4-methylpiperazin-1-yl)phenyl)-2-pyrazoline (2h) have proved to be potential antileukemic agents with remarkable cytotoxicity against HL-60 and K562 cells by activation of caspase 3, thereby inducing apoptosis.
RESUMO
In an endeavor to identify small molecules for the management of non-small-cell lung carcinoma, 10 new hydrazone derivatives (3a-j) were synthesized. MTT test was conducted to examine their cytotoxic activities against human lung adenocarcinoma (A549) and mouse embryonic fibroblast (L929) cells. Compounds 3a, 3e, 3g, and 3i were determined as selective antitumor agents on A549 cell line. Further studies were conducted to figure out their mode of action. Compounds 3a and 3g markedly induced apoptosis in A549 cells. However, both compounds did not show any significant inhibitory effect on Akt. On the other hand, in vitro experiments suggest that compounds 3e and 3i are potential anti-NSCLC agents acting through Akt inhibition. Furthermore, molecular docking studies revealed a unique binding mode for compound 3i (the strongest Akt inhibitor in this series), which interacts with both hinge region and acidic pocket of Akt2. However, it is understood that compounds 3a and 3g exert their cytotoxic and apoptotic effects on A549 cells via different pathway(s).
RESUMO
BACKGROUND: The purpose of this study is to investigate the effects of guided imagery on postoperative pain and comfort in geriatric orthopedics patients. METHODS: This study was carried out with a randomized-controlled true experimental design. The population of the study included geriatric patients receiving treatment at the orthopedics and traumatology inpatient clinic of a university hospital. Based on random selection, the sample consisted of total of 102 patients, including 40 patients in the experimental group and 40 in the control group. The data were collected using a Personal Information Form, the Visual Analog Scale, and the General Comfort Questionnaire. RESULTS: After the guided imagery intervention, the pain levels of the experimental group significantly decreased compared to their baseline pain levels (t = 4.002, P = 0.00). Their perceived comfort was also significantly improved (t = -5.428, P = 0.00). Although the perceived comfort of the control group decreased, this decrease was not statistically significant (t = 0.698, P = 0.489). CONCLUSION: It is recommended that guided imagery, which is an inexpensive and accessible method, be integrated into the nursing care process to reduce the pain and increase the comfort of geriatric orthopedics patients.
Assuntos
Procedimentos Ortopédicos , Ortopedia , Humanos , Idoso , Imagens, Psicoterapia/métodos , Dor Pós-Operatória/prevenção & controle , Medição da DorRESUMO
AIM: To evaluate the optimal timing and outcome of fluoroscopically guided transforaminal epidural steroid injections (TFESI) for the management of radicular pain due to extruded lumbar disc herniation (LDH). MATERIAL AND METHODS: In this clinical study, 305 individuals received fluoroscopically guided TFESI for the management of radicular pain due to extruded LDH. Preprocedural and 12-week postprocedural Visual Analog Scale (VAS) scores measuring radicular pain were statistically compared. The neurological conditions of the patients and the complications of the procedure were also recorded. RESULTS: The intensity of radicular pain evaluated by the mean preprocedural and 12-week postprocedural VASs were 8.765 ± 0.559 and 2.281 ± 0.401, respectively (p=0.001, and t=119.01). A correlation was noted between the short duration of symptoms before the procedure and the effectiveness of the procedure. After 12 weeks of the procedure, 32 of the 58 patients showed improvement in terms of neurological deficit. There was no major complication. Nine patients required lumbar disc surgery after the procedure. CONCLUSION: This clinical research demonstrated that TFESI for the management of extruded LDH may alleviate radicular pain and may decrease the neurological deficit and that it is more effective when performed at the earliest possible time point.
Assuntos
Deslocamento do Disco Intervertebral , Região Lombossacral , Humanos , Deslocamento do Disco Intervertebral/complicações , Dor , EsteroidesRESUMO
Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds 3b and 4a were found to be the most selective COX-1 inhibitors in this series with IC50 values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1H-Indol-3-yl)-N'-(4-morpholinobenzylidene)acetohydrazide (3b) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound 3b decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound 3b diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound 3b stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt , Relação Estrutura-Atividade , Ciclo-Oxigenase 1/metabolismoRESUMO
In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazole-hydrazone hybrids (1-15) were designed. An efficient procedure was employed for the synthesis of compounds 1-15. All hydrazones were subjected to an in vitro assay to assess their AR inhibitory profiles. Compounds 1-15 caused AR inhibition with Ki values ranging between 0.177 and 6.322 µM and IC50 values ranging between 0.210 and 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene)acetohydrazide (4) was the most potent inhibitor of AR in this series. Compound 4 markedly inhibited AR (IC50 = 0.297 µM) in a competitive manner (Ki = 0.177 µM) compared to epalrestat (Ki = 0.857 µM, IC50 = 0.267 µM). Based on the in vitro data obtained by applying the MTT test, compound 4 showed no cytotoxic activity toward normal (NIH/3T3) cells at the tested concentrations, indicating its safety as an AR inhibitor. Compound 4 exhibited proper interactions with crucial amino acid residues within the active site of AR. In silico QikProp data of all hydrazones (1-15) were also determined to assess their pharmacokinetic profiles. Taken together, compound 4 stands out as a promising inhibitor of AR for further in vivo studies.
Assuntos
Aldeído Redutase , Hidrazonas , Hidrazonas/farmacologia , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Aminoácidos , Simulação de Acoplamento MolecularRESUMO
AIM: To assess anterior gradient protein 2 (AGR2) gene expression in patients with human glioblastoma (GBM) in comparison to levels in healthy brain tissues. MATERIAL AND METHODS: We evaluated the expression levels of AGR2 gene in 34 tissue samples: 29 of them were derived from patients with glioblastoma (GBM group) and 5 were derived from patients with mesial temporal lobe epilepsy (control group). Moreover, in order to demonstrate the AGR2 gene expression, we performed RNA isolation from tissue samples, cDNA acquisition from RNA via reverse transcription and the demonstration of gene expression via real-time polymerase chain reaction. We therefore confirmed findings of both groups. RESULTS: The mean age of the GBM and control groups were 53.1 ± 12.82 years and 40.4 ± 10.92 years respectively. AGR2 gene expression levels of the GBM group were significantly higher than those of the control group (p < 0.01). There were no significant differences of AGR2 gene expression levels across age groups, levels of glucose, urea, creatinine, white blood cell count (WBC), neutrophil, lymphocyte, hemoglobin, platelet, thyroid-stimulating hormone (TSH), T3 and T4 in GBM group (p > 0.05). CONCLUSION: AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.