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2.
Pediatr Radiol ; 53(11): 2314-2319, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37599290

RESUMO

We aim to share the diagnostic methods and relevant findings of a rare case involving a 1-year-old girl with a variation of Shone syndrome, presenting with the coexistence of a single coronary artery and a fistula between the coronary artery and the right pulmonary artery. The patient had previously undergone aortic arch reconstruction surgery and during the preoperative evaluation, cardiac computed tomography angiography (CCTA) revealed the additional presence of a single coronary artery originating from the right, which fistulized into the right pulmonary artery distally. This finding was further confirmed by conventional angiography. This case report highlights the importance of CCTA in identifying and directing the treatment of additional anomalies that may accompany rare congenital abnormalities.

3.
Indian J Orthop ; 57(8): 1346, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37525727

RESUMO

[This corrects the article DOI: 10.1007/s43465-022-00800-7.].

4.
Cardiol Young ; 33(11): 2390-2392, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37203793

RESUMO

Ventriculoarterial connection is one of the important points of the segmental approach to congenital cardiac malformations. Double outlet of both ventricles is a rare form where both great arterial roots override the interventricular septum. In this article, we aimed to draw attention to this very rare form of ventriculoarterial connection by presenting an infant case diagnosed using echocardiography, CT angiography, and 3-dimensional modelling.


Assuntos
Cardiopatias Congênitas , Septo Interventricular , Lactente , Humanos , Cardiopatias Congênitas/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/anormalidades , Ecocardiografia/métodos , Artérias
5.
Cardiol Young ; 33(11): 2387-2389, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37194278

RESUMO

Mixed total anomalous pulmonary venous connection is a rare CHD with a wide variation in pulmonary venous anatomy and drainage. We present a ten-day-old newborn with a rare bizarre subtype of mixed total anomalous pulmonary venous connection.


Assuntos
Veias Pulmonares , Síndrome de Cimitarra , Recém-Nascido , Humanos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Veias Pulmonares/anormalidades , Síndrome de Cimitarra/diagnóstico por imagem , Síndrome de Cimitarra/cirurgia
7.
Indian J Orthop ; 57(2): 269-276, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36777129

RESUMO

Purpose: This study aims to find out the incidence, etiology, and risk factors, define clinical features, show the magnetic resonance imaging (MRI) and laboratory findings, and share the experience of treatment and clinical outcome of pregnancy-related sacral stress fractures (SSFs). Methods: In total, 29,291 (15,008 of them vaginal and 14,283 of them cesarean section delivery) women gave birth in our hospital between January 2016 and December 2021. Twenty-three of them (0.078%) who had low back and pelvic pain were diagnosed with SSFs using pelvic MRI. Dual-energy X-ray absorptiometry (DEXA) was used to rule out underlying osteopenia and osteoporosis and determine the type of SSFs. Results: The incidence of pregnancy-related SSFs was 0.078% (23/29,291patients). Six patients (26%) experienced pain during the last trimester of pregnancy, remaining seventeen (74%) patients had pain during the postpartum period. 73.91% of the patients were primigravida. Thirteen patients (56.52%) were classified as fatigue SSFs, eight (34.78%) were insufficiency SSFs, and only two (8.7%) were defined as a mixed type of SSFs. MRI imaging showed that nine patients (39.13%) had a left-sided fracture, seven patients (30.43%) had a right-sided fracture, and seven patients (30.43%) had bilateral fractures. Vitamin D deficiency (less than 20 ng/mL) was detected in seven patients (30.44%). One case had hypothyroidism in which thyroid stimulating hormone (TSH) was 5.41 µIU/mL. Conclusion: Pregnancy-related SSFs are uncommon but should be considered by clinicians in the differential diagnosis of low back and pelvic pain during pregnancy and the postpartum period. We determined that first pregnancy is a risk factor for SSFs. The current study also revealed that laboratory investigation of vitamin D deficiency and DEXA investigation, which may lead to osteoporosis or osteopenia, were crucial in the diagnosis. Furthermore, some SSFs should be reclassified as mixed fractures, fatigue, and insufficiency fractures.

8.
Ulus Travma Acil Cerrahi Derg ; 28(11): 1655-1658, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36282153

RESUMO

The pulmonary symptoms secondary to severe acute respiratory syndrome in coronavirus (COVID-19) infections are the most common presentation for the disease; however, it is now known that in a small portion of patients, severe hemorrhagic complications can also be seen. In this report, three cases of elderly women with known COVID-19 infection, developing spontaneous rectus sheath hematoma on anticoagulation therapy, are presented. Three cases presented above emphasize the need to perform a computed tomography examination after a sudden hemodynamic deterioration and a decrease in hemoglobin count in COVID-19 patients in intensive care units (ICUs). Since this clinical deterioration can be caused by spontaneous rectus sheath hematomas (RSH), it must be taken into consideration while examination. If these RSHs rupture into the abdominal cavity, the outcome may be fatal in few hours as represented in two of our cases. Major spontaneous hemorrhage in COVID-19 patients is quite uncommon; therefore, it may cause serious complications as it is rarely taken into consideration. Failure to acknowledge such a risk could significantly worsen the prognosis of the patients especially in ERs and ICUs.


Assuntos
COVID-19 , Doenças Musculares , Humanos , Feminino , Idoso , Reto do Abdome/diagnóstico por imagem , COVID-19/complicações , Hematoma/etiologia , Hematoma/complicações , Doenças Musculares/complicações , Doenças Musculares/terapia , Tomografia Computadorizada por Raios X , Anticoagulantes/efeitos adversos
9.
Gen Thorac Cardiovasc Surg ; 70(3): 295-297, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34846683

RESUMO

The incidence of subglottic stenosis after pediatric cardiac surgery is around 0.57-2.3%. An 11-year-old female patient, who underwent modified Blalock-Taussig shunt surgery at the age of 4 months, was interned for total repair of tetralogy of Fallot. Subglottic stenosis was revealed in preoperative examination with indirect laryngoscopy. Total repair of tetralogy of Fallot was performed under cardiopulmonary bypass support. While the patient was still on cardiopulmonary bypass support, subglottic stenosis was treated by holmium laser successfully without a complication. In suitable patients, cardiac and endoscopic laryngeal operations can be successfully and safely performed under cardiopulmonary bypass with a holmium laser.


Assuntos
Procedimento de Blalock-Taussig , Procedimentos Cirúrgicos Cardíacos , Lasers de Estado Sólido , Tetralogia de Fallot , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Constrição Patológica , Feminino , Humanos , Lactente , Lasers de Estado Sólido/uso terapêutico , Tetralogia de Fallot/cirurgia
10.
Int J Cardiovasc Imaging ; 38(2): 413-422, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34487310

RESUMO

The purpose of this study is to evaluate the radiation dose, image quality, and diagnostic accuracy of prospective ECG-gated cardiac CT at 70 kV and adaptive statistical iterative reconstruction (ASIR), with a single source, 512 slice MDCT in the diagnosis of complex congenital heart disease in infants. We retrospectively evaluated 47 infants (ages 1 day to 353 days) with prospective ECG-gated cardiac CT that was performed on a single source 512 slice CT at low tube voltage (70 kV) using a wide detector aperture, adaptive statistical iterative reconstruction algorithm (ASIR), and specific reconstruction software reducing coronary motion artifacts (SnapShot Freeze). All cardiac images were obtained during the first pass of contrast material through the anatomic structures of interest and the targets for the center of the acquisition window were set 45% of the R-R interval during one cardiac cycle without sedation and breath-hold. The median effective dose measured in our study was 0.64 ± 0.16 mSv. The average subjective overall image quality score was 4.34 ± 0.31 (range 3-5). For the determination of objective image quality, Mean Noise (HU), SNR, and CNR values ​​emerged as 20.8, 28.7(for pulmonary artery), and 27.1, respectively. Diagnostic accuracy was 100% for the main purposes for the main clinical indication. During cardiac CT examination, pathologies in addition to cardiac anomalies were found in 9/47 of cases (7 severe airway obstructions,1 posterior diaphragmatic hernia, 1 vertebral anomaly). Prospective ECG-gated cardiac CT scan at 70 kV and ASIR in infants with complex CHD provides low radiation dose (submillisievert) in a single heartbeat with a good objective and subjective image quality. It also provides important benefits in the diagnosis of additional pathology.


Assuntos
Cardiopatias Congênitas , Tomografia Computadorizada por Raios X , Angiografia Coronária/métodos , Eletrocardiografia/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Frequência Cardíaca , Humanos , Lactente , Valor Preditivo dos Testes , Estudos Prospectivos , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Estudos Retrospectivos
11.
Turk Gogus Kalp Damar Cerrahisi Derg ; 29(3): 399-403, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34589261

RESUMO

The increasing number of abdominal aortic grafts due to abdominal aortic aneurysms has caused secondary aortoenteric fistulas to be seen more frequently as a cause of gastrointestinal bleeding. High index of suspicion plays a significant role in the diagnosis in patients having clinical symptoms ranging from fecal occult blood to massive gastrointestinal bleeding, accompanied by hemorrhagic shock. A 65-year-old male patient developed two secondary aortoenteric fistulas consecutively. The first one was aortic graft-jejunal and the second one was aortic graft-duodenal in a short period. Secondary aortoenteric fistula developed after aortobifemoral bypass. The patient underwent graft revision and jejunal repair. He was reoperated three months later due to the newly developed aortic graft-duodenal fistula. The duodenal defect was closed, and an extra-anatomic aortoiliac bypass was performed to avoid graft-related enteric fistula. The patient was discharged uneventfully and was free from any complication at nine months after surgery.

12.
Cureus ; 13(5): e15265, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34189003

RESUMO

Objective With each passing day, dual-energy computed tomography (DECT) is being used more frequently in the evaluation of abdominal pathologies. In this article, we aimed to assess the role of dual-energy CT in locating gastrointestinal perforations, which are among the causes of acute abdomen. Materials and methods All patients who underwent DECT due to acute abdomen in a COVID-19 designated hospital between June 1st, 2020 and December 31st, 2020, who were found to have gastrointestinal tract (GIT) perforation and underwent surgery were included in the study. DECT results and intraoperative findings of the patients were compared. Results Thirteen patients (nine males and four females) who underwent DECT for acute abdomen and were diagnosed with perforation in the gastrointestinal system were included in the study. The mean age of the patients was 57.6 years (range: 11-85 years). Two patients had gastric perforation, three had duodenal perforations, and one patient had a perforation in the gallbladder wall. Two patients were diagnosed with jejunal perforations, one patient with Meckel's diverticulum, and three patients with colorectal perforation. Although free air was detected in the abdomen of one patient, perforation could not be located. In patients with GIT perforation who were operated on following DECT imaging, the perforation location shown on DECT correlated 100% with the perforation locations detected during surgery. Conclusion DECT is significantly effective in planning surgical treatment and determining the foci of perforation in GIT perforations.

13.
Pediatr Neurosurg ; 56(4): 379-384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33965938

RESUMO

INTRODUCTION: Trigonocephaly (TC), the tapering of the metopic suture toward the anterior, lateral inadequacy of supraorbital bar, hypoplasia of the ethmoid bone, and hypotelorism due to orbital medialization leads to a triangular shape in the head together with frontotemporal stenosis and widening of the biparietal diameter. Arachnoid cysts (ACs) are benign cysts, which are formed by cerebrospinal-fluid entrapment into the arachnoid membrane due to duplication or separation of the arachnoid membrane layers. ACs are typically located in the middle cranial fossa and Sylvian fissure region. They are mostly detected incidentally through neuroimaging. The coexistence of TC and AC is considerably rare; hence, its actual incidence is unknown. To our knowledge, the coexistence of nonsyndromic TC and AC has been revealed in only 2 publications in the literature. In this case study, 2 patients, one of whom were with unilateral and the other with bilateral temporally localized ACs, sizes of which increased following the reconstructive surgeries, and who underwent reconstructive surgery for TC, were presented. CASE REPORT: Both of the 2 patients that we have presented in our study are 7 months old and male. Fronto-orbital advancement and calvarial remodeling operations were performed on both. ACs of the patients were not intervened. However, in the post-op follow-ups, the left temporal cyst of the 1st case and the right cyst of the 2nd case grew radiologically, and the left cyst became very small. DISCUSSION/CONCLUSION: TC must be treated surgically. ACs may show changes in size secondary to the increase in intracranial volume following reconstructive surgery for TC. However, if it does not give rise to any complaints, it can be followed-up clinically and radiologically. Patients should be followed-up for many years, given that neurodevelopmental and behavioral problems may occur later in both pathologies.


Assuntos
Cistos Aracnóideos , Craniossinostoses , Procedimentos de Cirurgia Plástica , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/cirurgia , Suturas Cranianas , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Humanos , Lactente , Masculino , Lobo Temporal
14.
Case Rep Radiol ; 2021: 6657447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815859

RESUMO

Fistulous communications between the ventricular cavities and the coronary arterial tree can be found in the presence of hypoplasia of the left ventricle, especially when the ventricular septum is intact and mitral stenosis and aortic atresia subtype are present. The cardiac CT provides excellent anatomic information especially in the evaluation of extracardiac vessels and coronary arteries. In this case study, we report a newborn with ventriculocoronary fistulas (VCFs) with the hypoplastic left disease diagnosed with cardiac CT. Transthoracic echocardiography of a term baby showed hypoplastic left heart syndrome (HLHS) with mitral stenosis and aortic atresia. The patient immediately underwent a Sano variation of the Norwood procedure. On the postoperative second day, the clinical status of the patient deteriorated. A prospective electrocardiogram-gated axial technique was performed within a single heartbeat for the patient and large VCFs were detected and a second operation were performed to close the VCFs that failed. On the nineteenth day after the operation, the baby passed away. According to us, cardiac CT can also be performed free-breathing and without anesthesia in the neonatal period for the definition of complex cardiac anatomy with the lower radiation dose from the latest scanners, radiation risk of CT should be weighed against the anesthesia risk of cardiac MRI and intraoperative risk of conventional cardiac angiography. Pre-operative cardiac CT may increase surgical success.

15.
Cureus ; 13(3): e13676, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33824827

RESUMO

Objective The aim of this study was to discuss the results of craniometric measurements and surgical treatments in patients operated for isolated trigonocephaly (TC) in light of the current literature. Methods A total of 18 cases who underwent surgery for isolated TC were included in the study. Age, gender, family history, follow-up time, complications, duration of surgery, surgical blood loss, and amount of blood replacement in these patients were recorded. Craniometric measurements such as metopic angle (MA), cephalic index (CI), interparietal distance (IPD), intercoronal distance (ICD), and their ratio to each other were evaluated according to pre-and postoperative parameters. Photographs of the patients were taken before and after the operation. The Whitaker classification and Kampf "aesthetic outcome staging" were used in the evaluations. Results The mean MA values after the operation increased to reach above 147 degrees in all cases. The average CI did not change. ICD measurement averages increased significantly. The average IPD/ICD ratio decreased due to the increase in ICD and the enlargement of the anterior fossa after the operation. According to the Whitaker classification and Kampf "aesthetic outcome staging" scale, 17 of our cases were at stage I, rated as perfect, and one was at stage II, rated as good. Conclusion Surgery performed at the appropriate time for TC yields cosmetically satisfactory results. Since potential neurological and cognitive morbidities occur mostly in school-age patients, long-term follow-up of the cases is required. Performing craniometric measurements enables patients to be evaluated with objective and measurable numerical data.

16.
Radiol Case Rep ; 16(3): 575-578, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33408800

RESUMO

We present a case of a dilated right ventricular outflow tract (RVOT) in a 30-year-old woman because of localized constrictive pericarditis where the diagnosis was reached with the help of cardiac CT, and MRI. The patient was suffering from congestive heart failure for two years and had partial pericardiectomy 10 years ago. The diagnostic evaluation of the localized pericarditis requires a multimodality approach and suspected patients would benefit from simple tests, such as X-ray and echocardiography, but also furthermore complex imaging, including cardiac CT and MRI. To our knowledge, our case is the second case in the literature that show localized constrictive pericarditis presenting with giant RVOT and this is the first case that cardiac CT and MRI have been performed.

17.
Environ Pollut ; 255(Pt 2): 113318, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610501

RESUMO

Bisphenol A (BPA), as synthetic monomer used in the production of polycarbonate plastic and epoxy resins, has endocrine disruptor properties and high risk on human health. Epigenetic alterations could act an important role in BPA-induced toxicity, but its mechanism has not been fully understood. We investigated the effects of BPA on gene expression of chromatin modifying enzymes, promoter methylation of tumor suppressor genes and histone modifications in human prostate carcinoma cells (PC-3). IC50 value of BPA was determined as 217 and 190 µM in PC-3 cells by MTT and NRU tests, respectively. We revealed an increase in global levels of 5-methylcytocine and 5-hydroxymethylcytocine at 10 µM of BPA for 96 h. We observed a significant increase on promoter DNA methylation and decrease on gene expression of p16 gene while no change was observed for Cyclin D2 and Rassf1. Significant changes were observed in global histone modifications (H3K9ac, H3K9me3, H3K27me3, and H4K20me3) in PC-3 cells. According to these results, we investigated wide-range epigenetic modifications using PCR arrays. After 96 h BPA exposure, chromatin modifying enzymes including KDM5B and NSD1 were significantly downregulated. Also, promoter methylation of tumor suppressor genes including BCR, GSTP1, LOX, MGMT, NEUROG1, PDLIM4, PTGS2, PYCARD, TIMP3, TSC2 and ZMYDN10 altered significantly. ChIP results showed that H3K9ac, H3K9me3 and H3K27me3 modifications on p16 gene showed significant increases after 1 and 10 µM of BPA exposure. In conclusion, epigenetic signatures such as DNA methylation and histone modifications could be proposed as molecular biomarkers of BPA-induced prostate cancer progression.


Assuntos
Compostos Benzidrílicos/toxicidade , Metilação de DNA/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Código das Histonas/efeitos dos fármacos , Fenóis/toxicidade , Neoplasias da Próstata/induzido quimicamente , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Linhagem Celular Tumoral , Ciclina D2/biossíntese , Ciclina D2/genética , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células PC-3 , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Processamento de Proteína Pós-Traducional , Inibidor Tecidual de Metaloproteinase-3 , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética
18.
Biochim Biophys Acta Mol Cell Res ; 1865(12): 1934-1944, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30290242

RESUMO

The aim of this study was to investigate the molecular mechanism of pancreatic islet-derived mesenchymal stem cell (PID-MSC) differentiation into beta-cells in the presence of insulin and leptin resistance stimulators. We determined that beta-cell differentiation was stimulated by glucose, insulin, and leptin. Co-administration of insulin and leptin resulted in greater, at a further stage of differentiation but non-functional beta-cell formation. The levels of p-AKT(Ser473) did not change; SOCS3, PTP1B, p-IRS1(Ser307), PTEN levels increased and p-IRS1(Try) levels decreased due to insulin and leptin co-administration. These findings suggest that co-administration of insulin and leptin to PID-MSCs results in the development of both insulin and leptin resistance together. We showed that this differentiation signaling is mainly mediated by AKT/GSK-3ß/ß-catenin and Tub. Moreover, ß-catenin and Tub were linked to each other in the nucleus under this condition. Furthermore, we found that Tub and ß-catenin contributes to insulin production by increasing the expression of transcription factors by binding to the promoter regions of ins1, ins2, and pdx1 genes. In addition, Tub is also bound to the promoter region of the MafA gene. These findings demonstrate that when insulin and leptin resistance develop together in rat PID-MSCs beta-cell differentiation increases markedly via ß-catenin and Tub. New therapeutic agents that inhibit AKT/GSK-3ß/ß-catenin and in particular Tub may help prevent the development or retard the progression of type 2 diabetes.


Assuntos
Resistência à Insulina , Células Secretoras de Insulina/citologia , Leptina/farmacologia , Células-Tronco Mesenquimais/citologia , Proteínas/metabolismo , Transdução de Sinais , beta Catenina/metabolismo , Animais , Diferenciação Celular , Núcleo Celular/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Insulina/farmacologia , Células Secretoras de Insulina/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo
19.
J Cell Biochem ; 119(7): 6274-6287, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29663501

RESUMO

Altered or aberrant glycosylation is a common phenomenon in cancer cells and it originates from changes in the expression of the enzymes, glycosyltransferase, and glycosidase which up-regulate in response to some oncogenes in the glycan synthesis pathway. In this present study, it has been aimed to determine the alteration of sialic acid and fucose expressions in the cell surface of human thyroid carcinoma cells and investigate the changes in tumorigenic and malignant characters after treating them with specific plant lectins. Our study showed that the cell surface glycan chains of anaplastic 8305C, follicular FTC-133, and papillary K1 thyroid carcinoma cells were rich in α-2,6, α-2,3, sialic acid, and α-1,6 fucose residues. When the cells were treated with specific doses of Maackia amurensis lectin II (MAL), Sambucus nigra agglutinin (SNA), and Aleuria aurantia lectin (AAL) which have specific binding capacity for the detected glycan residues, respectively their cancerous traits changed dramatically. Remarkable findings obtained from MAL treatment leading to necrosis in 8505C cells without any toxicity for normal thyroid epithelial cells but it had proliferative effect on K1 and FCT-133 cells. Besides, MAL and SNA treatment decreased the mobility of 8505C and K1 cells. MAL and SNA lectins dramatically reduced the endothelial affinity of the cells and AAL significantly attenuated that of 8050C and K1 cells but not FTC-133. These results suggest that altered cell surface glycosylation in thyroid cancer seems to be a strong candidate for developing new therapeutic strategies.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Lectinas/farmacologia , Fito-Hemaglutininas/farmacologia , Lectinas de Plantas/farmacologia , Proteínas Inativadoras de Ribossomos/farmacologia , Neoplasias da Glândula Tireoide/patologia , Movimento Celular/efeitos dos fármacos , Humanos , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Células Tumorais Cultivadas
20.
Chronobiol Int ; 35(5): 705-718, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29400578

RESUMO

The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.


Assuntos
Antineoplásicos/administração & dosagem , Cronofarmacoterapia , Everolimo/administração & dosagem , Sistema Imunitário/efeitos dos fármacos , Imunossupressores/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Antineoplásicos/toxicidade , Everolimo/toxicidade , Feminino , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Imunossupressores/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Inibidores de Proteínas Quinases/toxicidade , Fatores Sexuais , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Serina-Treonina Quinases TOR/metabolismo , Timo/efeitos dos fármacos , Timo/imunologia , Timo/patologia , Fatores de Tempo
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