RESUMEN
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.
Asunto(s)
COVID-19 , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Enfermedad Crónica , Tos/etiología , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Transversales , Turquía/epidemiologíaRESUMEN
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. There is a misconception that use of isotretinoin increases risk of suicide. METHODS: We used the terms 'isotretinoin suicide' and 'acne treatment suicide' to search YouTube videos. Videos that were not in English, were irrelevant, or were 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: In total, 200 videos were examined and 112 videos were included in the study. Of these, 39 videos (34.8%) were found to be reliable, and 73 videos (65.2%) were found to be unreliable. The DISCERN values of videos uploaded by physicians or professional organizations, and health information websites were found to be significantly higher. There were statistically significant negative correlations between DISCERN score and both video length and the length of time the video was on YouTube, while a positive correlation was observed between DISCERN score and the number of subscribers. CONCLUSIONS: Although videos created by dermatologists have become widespread in recent years, they are still insufficient. Patient experience videos mostly contain information that does not reflect reality, and they 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.
Asunto(s)
Acné Vulgar , Fármacos Dermatológicos , Isotretinoína , Medios de Comunicación Sociales , Suicidio , Grabación en Video , Isotretinoína/efectos adversos , Isotretinoína/uso terapéutico , Humanos , Acné Vulgar/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Reproducibilidad de los Resultados , Información de Salud al Consumidor/normasRESUMEN
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.
Asunto(s)
Quemaduras , Alta del Paciente , Humanos , Estudios Transversales , Femenino , Masculino , Quemaduras/terapia , Quemaduras/psicología , Adulto , Turquía , Alta del Paciente/estadística & datos numéricos , Alta del Paciente/normas , Persona de Mediana Edad , Encuestas y Cuestionarios , Anciano , Evaluación de Necesidades/estadística & datos numéricosRESUMEN
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.
Asunto(s)
Aldehído Reductasa , Hidrazonas , Hidrazonas/farmacología , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Aminoácidos , Simulación del Acoplamiento MolecularRESUMEN
In an attempt to identify potent antitumor agents for the fight against non-small cell lung cancer, new thiazolyl hydrazones (2a-n) were synthesized and examined for their in vitro cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells by means of the MTT assay. Furthermore, the effects of the most potent anticancer agents on apoptosis and Akt inhibition were investigated. 2-[2-((Isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methylsulfonylphenyl)thiazole (2k) (IC50 = 1.43 ± 0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(1,3-benzodioxol-5-yl)thiazole (2l) (IC50 = 1.75 ± 0.07 µM) displayed more pronounced anticancer activity than cisplatin (IC50 = 3.90 ± 0.10 µM) on A549 cell lines; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methoxyphenyl)thiazole (2j) (IC50 = 3.93 ± 0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis in A549 cells. Compound 2j (IC50 = 3.55 ± 0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC50 = 4.93 ± 0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC50 concentrations (1.43 and 1.75 µM, respectively). To comprehensively elucidate the binding pose of compound 2j and to provide a detailed understanding on the ligand' binding mechanism, induced-fit docking calculations were also conducted. Both in vitro and in silico studies suggest that compound 2j shows its cytotoxic and apoptotic effects on A549 cell lines via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways.
Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Proteínas Proto-Oncogénicas c-akt , Tiazoles/farmacología , Tiazoles/química , Hidrazonas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Estructura Molecular , Línea Celular TumoralRESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Inhibidores de la Angiogénesis/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Simulación del Acoplamiento Molecular , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt , Relación Estructura-Actividad , Ciclooxigenasa 1/metabolismoRESUMEN
OBJECTIVE: This study aimed to detect which of the two main medicines suggested in the treatment of postligation cardiac syndrome (PLCS)-dobutamine or mirinone-possesses a more therapeutic effect. While doing this, clinicians are provided with a broader perspective on the treatment and follow-up of cases. The desire was to increase the treatability and monitor ability of the cases in question and hence their survivability. STUDY DESIGN: A retrospective review of a cohort of infants with PLCS was conducted between March 2012 and December 2018. In the treatment of infants with PLCS, dobutamine (dobutamine study group-DSG) or milrinone (milrinone study group-MSG) was used. The respiration, cardiac, echocardiography, and perfusion parameters of the cases were assessed both before and after ligation. Based on the data obtained, both the effects of the medicines on PLCS and the difference between their therapeutic effects were studied. The accuracy of prognostication was assessed with receiver operating characteristic analyses. RESULTS: PLCS was detected in 29 (34.1%) of 85 patent ductus arteriosus ligation cases in total. Of all the PLCS cases, 13 (44.8%) were treated with dobutamine and 16 (55.2%) with milrinone. It was observed that the effects of the medicines on the respiratory system and cardiovascular system manifested in the third and 6th hour, respectively. It was detected that both medicines had more effect on the systolic blood pressure (SBP) (area under the curve [AUC]: 0.997/0.996, p = 0.001/0.002) than on the diastolic blood pressure (AUC: 0.911/0.843, p = 0.032/0.046). CONCLUSION: Dobutamine and milrinone, two primary medicines that can be used in the treatment of cases with PLCS, possess similar therapeutic effects on this pathology. In addition, their postoperative therapeutic effects on the SBP are more in the foreground.
Asunto(s)
Cardiotónicos/administración & dosificación , Sistema Cardiovascular/efectos de los fármacos , Dobutamina/administración & dosificación , Milrinona/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Gasto Cardíaco/efectos de los fármacos , Conducto Arterioso Permeable/cirugía , Ecocardiografía , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Ligadura , Masculino , Respiración/efectos de los fármacos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In an endeavor to identify potent anti-inflammatory agents, new thiosemicarbazones (TSCs) incorporated into a diaryl ether framework (2a-2l) were prepared and screened for their in vitro inhibitory effects on cyclooxygenases (COXs). 4-[4-(Piperidin-1-ylsulfonyl)phenyl]-1-[4-(4-cyanophenoxy)benzylidene]thiosemicarbazide (2c) was the most potent and selective COX-1 inhibitor in this series, with an IC50 value of 1.89 ± 0.04 µM. On the other hand, 4-[4-(piperidin-1-ylsulfonyl)phenyl]-1-[4-(4-nitrophenoxy)benzylidene]thiosemicarbazide (2b) was identified as a nonselective COX inhibitor (COX-1 IC50 = 13.44 ± 0.65 µM, COX-2 IC50 = 12.60 ± 0.78 µM). Based on molecular docking studies, the diaryl ether and the TSC groups serve as crucial moieties for interactions with pivotal amino acid residues in the active sites of COXs. According to MTT test, compounds 2b and 2c showed low cytotoxic activity toward NIH/3T3 cells. Their in vivo anti-inflammatory and antioxidant potencies were also assessed using the lipopolysaccharide-induced sepsis model. Compounds 2b and 2c diminished high-sensitivity C-reactive protein, myeloperoxidase, nitric oxide, and malondialdehyde levels. Both compounds also caused a significant decrease in aspartate aminotransferase levels as well as alanine aminotransferase levels. In silico pharmacokinetic studies suggest that compounds 2b and 2c possess favorable drug-likeness and oral bioavailability. It can be concluded that these compounds may act as orally bioavailable anti-inflammatory and antioxidant agents.
Asunto(s)
Tiosemicarbazonas , Animales , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Éteres , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Tiosemicarbazonas/farmacologíaRESUMEN
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death throughout the world. Due to the shortcomings of traditional chemotherapy, targeted therapies have come into prominence for the management of NSCLC. In particular, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy has emerged as a first-line therapy for NSCLC patients with EGFR-activating mutations. In this context, new indenopyrazoles, which were prepared by an efficient microwave-assisted method, were subjected to in silico and in vitro assays to evaluate their potency as EGFR TK-targeted anti-NSCLC agents. Compound 4 was the most promising antitumor agent towards A549 human lung adenocarcinoma cells, with an IC50 value of 6.13 µM compared to erlotinib (IC50 = 19.67 µM). Based on its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), it can be concluded that compound 4 exerts selective antitumor action. This compound also inhibited EGFR TK with an IC50 value of 17.58 µM compared to erlotinib (IC50 = 0.04 µM) and induced apoptosis (56.30%). Taking into account in silico and in vitro data, compound 4 stands out as a potential EGFR TKI for the treatment of NSCLC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirazoles/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Simulación por Computador , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib/farmacología , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacocinética , Pirazoles/química , Pirazoles/farmacocinéticaRESUMEN
Recently, COVID-19 has appeared as an international pandemic, leading to serious risks for humans. Using face masks is one of the most common measures in a wide-ranging prevention program that could control the COVID-19 dissemination. Face masks are typically composed of non-biodegradable and non-renewable polymers based on petroleum, which are harmful to nature and lead to health problems. In the present study, disposable face masks, the use of which has increased due to the Covid-19 pandemic throughout the world and which cause environmental pollution, were divided into very small pieces and utilized as a modifier in the bitumen binder. Therefore, this study aimed to provide a solution to such a significant environmental problem. Five different ratios of waste mask and the single ratio of styrene-butadienestyrene (SBS) were added to the pure binder and the rheological, physical, and chemical properties of the modified binders were compared. The result showed that adding a waste mask and SBS to the pure bitumen caused increases in binders' softening point and viscosity and reductions in the penetration value. Waste mask modifications were able to better maintain its elastic properties both at low stress and high-stress levels with increasing temperature. 3% SBS was the binder most affected by temperature rise. As a result, it has been determined that binders containing more than 2% waste mask have better performance characteristics than binders containing 3% SBS in terms of physical and rheological properties.
RESUMEN
Inadequate immunosuppressive therapy causes rejection, whereas an overdose may lead to infections or malignancy to affect a patient's life and comfort. This study used a descriptive correlational design to determine how compliance with immunosuppressive therapy affected the well-being of liver transplant patients. The study was conducted in the liver transplant unit of a university hospital with 103 patients who underwent liver transplant surgery. The target population included patients who received treatment in liver transplant clinics between July 2016 and August 2017. Mean age of the patients in the study was 44.66 ± 14.86 years and the time after transplant was 15.48 ± 16.90 months on the average. A significant difference was found between mean General Comfort Scale scores according to the variable of adherence status (t = 6.898, p < .05). Simple linear regression analysis showed a positive moderate, significant correlation between the adherence variable and mean General Comfort Scale scores (R = 0.543, p < .001). It was found that the patients who adhered to immunosuppressive therapy experienced higher levels of comfort. Therefore, arrangements to improve patient adherence to therapy, hence comfort, are recommended, as well as periodic evaluations of patient comfort levels.
Asunto(s)
Inmunosupresores , Trasplante de Hígado , Adulto , Estudios Transversales , Humanos , Inmunosupresores/uso terapéutico , Hígado , Cumplimiento de la Medicación , Persona de Mediana EdadRESUMEN
This study was carried out in a university hospital located in the southeastern region of Turkey to determine the relationship between the perceived stress with the religious attitude and behavior of the intensive care patient's relatives; 150 patient's relatives participated in this descriptive and relation-seeking study between the dates of January and April 2019. The Personal Data Form, Perceived Stress Scale, and Religious Attitude and Behavior Inventory that were designed by their own researchers as a result of the literature review were used in this study. As a result of this study, it was found that there was a statistically significant relationship between religious attitude and behavior and perceived stress levels of the patient's relatives with sociodemographic features such as age, gender, marital status, and educational level. It was determined that the participants mostly prefer to pray as a method for stress management (65.3%). In terms of educational level, it was identified that 42% of the participants are elementary school graduates; besides, the stress level of this group was significantly lower than the others, and their religious attitude and behaviors were higher (p = 0.004). In consideration of these results, in terms of holistic care, it is recommended that nurses should make arrangements toward their strategy for stress management considering the religious attitudes and behaviors of patients' relatives.
Asunto(s)
Actitud , Cuidados Críticos , Escolaridad , Humanos , Encuestas y Cuestionarios , TurquíaRESUMEN
Aldose reductase (AR) catalyzes the NADPH-dependent reduction of glucose to sorbitol in the polyol pathway, which plays an important role in the development of diabetic complications including cataract, retinopathy, nephropathy, and neuropathy. AR has been considered as an important target to heal these long-term diabetic complications and for this reason the development of new AR inhibitors is an important approach in modern medicinal chemistry. In the current study, new 4-aryl-2-[2-((3,4-dihydro-2H-1,5-benzodioxepine-7-yl)methylene)hydrazinyl]thiazole derivatives (1-12) were synthesized and screened for their inhibitory effects on AR which was purified by diverse chromatographic methods with a yield of 1.40% and a specific activity of 2.00 EU/mg. All compounds were determined as promising AR inhibitors with the Ki values in the range of 0.018 ± 0.005 µM-3.746 ± 1.321 µM compared to the quercetin (Ki = 7.025 ± 1.780 µM). In particular, 4-(4-cyanophenyl)-2-[2-((3,4-dihydro-2H-1,5-benzodioxepin-7-yl)methylene)hydrazinyl]thiazole (3) was detected as the most potential AR inhibitor in this series with the Ki value of 0.018 ± 0.005 µM and the compound showed competitive AR inhibition. The cytotoxic effects of compounds 1-12 were investigated on L929 mouse fibroblast (healthy) cells using MTT assay and all these compounds were defined as non-cytotoxic agents against L929 cells. Molecular docking studies, which were employed to determine the affinity of compounds 1-12 into the active site of AR, highlighted that the thiazole scaffold of all these compounds presented π-π stacking interactions with Trp20 and Phe122. According to both in vitro and in silico assays, these potential AR inhibitors may have great importance in the prevention of diabetic microvascular conditions.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Tiazoles/farmacología , Aldehído Reductasa/metabolismo , Animales , Células Cultivadas , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/químicaRESUMEN
Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a-i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a-i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 µM, 9.62 ± 1.14 µM, and 8.07 ± 1.36 µM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 µM, 19.41 ± 2.38 µM, and 23.81 ± 4.17 µM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 µM when compared with erlotinib (IC50 = 0.04 ± 0.01 µM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Indoles/farmacología , Oxadiazoles/farmacología , Células A549 , Sitio Alostérico , Animales , Apoptosis , Benzotiazoles/química , Dominio Catalítico , Línea Celular Tumoral , Ciclooxigenasa 1/química , Ciclooxigenasa 2/química , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib/farmacología , Células HCT116 , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Estructura Molecular , Ovinos , Relación Estructura-Actividad , Tiazoles/químicaRESUMEN
POLQ is a unique multifunctional replication and repair gene that encodes for a N-terminal superfamily 2 helicase and a C-terminal A-family polymerase. Although the function of the polymerase domain has been investigated, little is understood regarding the helicase domain. Multiple studies have reported that polymerase θ-helicase (Polθ-helicase) is unable to unwind DNA. However, it exhibits ATPase activity that is stimulated by single-stranded DNA, which presents a biochemical conundrum. In contrast to previous reports, we demonstrate that Polθ-helicase (residues 1-894) efficiently unwinds DNA with 3'-5' polarity, including DNA with 3' or 5' overhangs, blunt-ended DNA, and replication forks. Polθ-helicase also efficiently unwinds RNA-DNA hybrids and exhibits a preference for unwinding the lagging strand at replication forks, similar to related HELQ helicase. Finally, we find that Polθ-helicase can facilitate strand displacement synthesis by Polθ-polymerase, suggesting a plausible function for the helicase domain. Taken together, these findings indicate nucleic acid unwinding as a relevant activity for Polθ in replication repair.
Asunto(s)
ADN Helicasas/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Secuencia de Aminoácidos , Cristalografía por Rayos X , ADN/metabolismo , Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades/fisiología , Replicación del ADN/fisiología , ADN de Cadena Simple/metabolismo , ADN Polimerasa Dirigida por ADN/fisiología , Humanos , Hibridación de Ácido Nucleico , Unión Proteica , Recombinación Genética/genética , ADN Polimerasa thetaRESUMEN
BACKGROUND AND AIM OF THE STUDY: In vitro studies have shown a reduction in radial artery spasm with the use of calcium antagonists. The purpose of this study was to evaluate the efficacy of topical treatment of the radial artery conduit using either verapamil or nicardipine before the anastomoses. METHODS: This prospective randomized study included 131 patients, who underwent coronary artery bypass grafting surgery with the use of the radial artery as a conduit. In 65 patients, the harvested radial artery was topically treated with verapamil and in 66 patients with nicardipine. After harvesting the radial artery, the direct flow through the conduit was measured in vitro before 5-minute incubation in nicardipine or verapamil and measured again after incubation. The flow before and after incubation was compared. Postincubation flow was also compared in the two groups. After performing the anastomosis, the flow through the radial artery was measured in vivo. RESULTS: The mean flow after NaCl incubation was 19.93 ± 12.66 mL/min and after incubation in the Ca+ channel blocker 47.16 ± 14.58 mL/min (P < .001). No significant difference in postincubation free flow was found between verapamil (46.29 ± 15.43 mL/min) and nicardipine (48.01 ± 13.77 mL/min; P = .503). CONCLUSION: Topical treatment with Ca+ channel blockers reduces radial artery spasm and significantly increases the free flow through the radial artery conduit. Nicardipine is a safe and effective alternative of verapamil in preventing spasm of radial artery conduit.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Puente de Arteria Coronaria/efectos adversos , Nicardipino/uso terapéutico , Arteria Radial/trasplante , Espasmo/prevención & control , Enfermedades Vasculares/prevención & control , Verapamilo/uso terapéutico , Administración Tópica , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arteria Radial/efectos de los fármacos , Arteria Radial/fisiopatología , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVE: Intraventricular hemorrhage (IVH) is an important problem in neonatal units not only in terms of its consequences but also its follow-up and the prediction of its emergence in newborns. In this study, we have compared platelet parameters such as platelet count (PC), mean platelet volume (MPV), and platelet mass index (PMI) in terms of IHV in very-low-birth-weight (VLBW) newborns. Thus, we have tried to determine platelet values to guide clinicians in both the prediction and follow-up of IVH. STUDY DESIGN: This is a retrospective, multicenter, and case-controlled study. In this study, 386 cases of VLBW newborns (below 1,500 g) and gestational age below 32 weeks, hospitalized and monitored between August 8, 2012, and April 7, 2018, were included. The platelet values of the cases on their 12th hour postpartum (PC1, MPV1, and PMI1) and the platelet values on days 5 to 7 (PC2, MPV2, and PMI2) were recorded in their study cards. A p-value of <0.05 was accepted as statistically significant. RESULTS: While there was no difference of PC1, MPV1, PMI1, PC2, or MPV2 values (p > 0.05), PMI2 values in the severe stage IVH group cases were found to be significantly lower compared with other platelet parameters (p < 0.05). CONCLUSION: PMI2 values can provide clinicians with important knowledge that may aid them in recognizing important pathologies such as IVH.
Asunto(s)
Plaquetas/citología , Hemorragia Cerebral Intraventricular/sangre , Enfermedades del Prematuro/sangre , Recien Nacido Prematuro/sangre , Volúmen Plaquetario Medio , Recuento de Plaquetas , Estudios de Casos y Controles , Hemorragia Cerebral Intraventricular/diagnóstico , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the effect of pretreatment with obestatin (OB), an endogenous hormone also found in mother's milk, in experimental necrotizing enterocolitis (NEC). STUDY DESIGN: Pups were randomized into four groups: control, OB-control, NEC, and OB-NEC. NEC was induced by asphyxia and hypothermia in the NEC and OB-NEC groups. OB was administered to the OB-control and OB-NEC groups. Macroscopic scoring of the intestinal tract was evaluated and tissue samples were obtained for histopathological and biochemical examination on the fourth day. RESULTS: OB improved the macroscopic appearance of the gut and the clinical score during the experiment (p < 0.05). The rate of occurrence of NEC in the OB-NEC group was lower than the NEC group (p = 0.001). OB prevented necrosis and reduced the number of apoptotic cells in the OB-NEC group compared with the NEC group (p = 0.006). Furthermore, interleukin-6 and malondialdehyde levels in the OB-NEC group were lower than the NEC group (p < 0.05). CONCLUSION: OB reduced intestinal damage and prevented necrosis through anti-inflammatory and antiapoptotic effects in experimental NEC. This effect of OB should be confirmed in clinical studies. Furthermore, future research should investigate whether OB plays a role in NEC pathogenesis or NEC is associated with OB levels in the serum and in breast milk.
Asunto(s)
Enterocolitis Necrotizante/tratamiento farmacológico , Ghrelina/uso terapéutico , Intestinos/patología , Animales , Animales Recién Nacidos , Apoptosis , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/fisiopatología , Ghrelina/farmacología , Intestinos/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Patients who have secondary pseudohypoaldosteronism (PHA) in addition to hyponatraemia, hyperpotassaemia and high serum aldosterone levels for the age were included in this retrospective study.Among eight patients, seven patients were diagnosed with PHA secondary to obstructive uropathy (OUP), whereas one patient had PHA secondary to ileostomy. Six patients with OUP had simultaneous urinary tract infection (UTI) and in all except one patient, secondary PHA recovered with only UTI treatment before applying surgical correction. All the patients were younger than 3 months age. In three patients with PUV diagnosis, salt wasting recurred in an UTI episode under 3 months of age.
Asunto(s)
Aldosterona/sangre , Hiperpotasemia , Hiponatremia , Seudohipoaldosteronismo , Infecciones Urinarias , Anomalías Urogenitales , Desequilibrio Hidroelectrolítico , Diagnóstico Diferencial , Femenino , Humanos , Hiperpotasemia/diagnóstico , Hiperpotasemia/etiología , Hiponatremia/diagnóstico , Hiponatremia/etiología , Lactante , Masculino , Natriuresis , Seudohipoaldosteronismo/diagnóstico , Seudohipoaldosteronismo/etiología , Seudohipoaldosteronismo/metabolismo , Seudohipoaldosteronismo/terapia , Estudios Retrospectivos , Turquía , Infecciones Urinarias/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/metabolismo , Anomalías Urogenitales/complicaciones , Anomalías Urogenitales/metabolismo , Anomalías Urogenitales/cirugía , Desequilibrio Hidroelectrolítico/diagnóstico , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
The aim of this study was to evaluate the therapeutic effect of lycopene on a hyperoxia-induced lung injury model in rat pups. Full-term rat pups were included in the study 12-24 h after delivery. The pups were separated into 4 groups: normoxia control (NC), hyperoxia control (HC), hyperoxia + lycopene (HL), and normoxia lycopene (NL). The normoxia groups were housed in ambient air, and the hyperoxia groups in > 85% O2. HL and NL groups received 50 mg lycopene in oil/kg body weight/day delivered intraperitoneally (i.p.), the other groups received oil alone. On day 11, the rat pups were sacrificed and their lungs removed. Statistically significant injury was observed in all histological parameters measured (MLI, proliferating cell nuclear antigen (PCNA), and apoptosis) in the HC group (HC vs NC, p = 0.001). This injury could not be reversed with lycopene treatment (HC vs HL, 0.05; NC vs HL, p = 0.001). With hyperoxia, statistically significant decreases were observed in biochemical parameters in terms of SOD, MDA, and IL-6 values (HC vs NC: SOD, p = 0.02; MDA, p = 0.043; IL-6, p = 0.001). The use of lycopene did not provide any improvement in these values (HC vs HL, p > 0.05). Hyperoxia or lycopene had no effect on IL-1ß and GPx (p > 0.05). When comparing NC and NL groups, negative effects were observed in the group given lycopene in terms of MLI, PCNA, apoptosis, and IL-6 (all parameters, p = 0.001). We observed that 50 mg lycopene in oil/kg body weight/day given via i.p. had no curative effect on the hyperoxia-induced lung injury in newborn rats and may even induce adverse effects.