RESUMO
Leishmania spp. comprises a group of protozoan parasites that affect millions of people around the world. Understanding the main cell cycle-dependent events could provide an important route for developing specific therapies since some factors involved in cell cycle control may have low similarity relative to their homologs in mammals. Furthermore, accurate cell cycle-dependent analyses often require many cells, which can be achieved through cell cycle synchronization. Here, we described a useful method to synchronize procyclic promastigote forms of Leishmania amazonensis using hydroxyurea (HU) and the analysis of its DNA content profile. This approach can be extended to other trypanosomatids, such as Trypanosoma cruzi or Trypanosoma brucei, and provides an effective method for arresting more than 80% of cells at the G1/S phase transition.
Assuntos
Leishmania mexicana , Leishmania , Animais , Ciclo Celular , Divisão Celular , Humanos , Hidroxiureia/farmacologia , Leishmania/metabolismo , MamíferosRESUMO
Leishmaniases belong to the inglorious group of neglected tropical diseases, presenting different degrees of manifestations severity. It is caused by the transmission of more than 20 species of parasites of the Leishmania genus. Nevertheless, the disease remains on the priority list for developing new treatments, since it affects millions in a vast geographical area, especially low-income people. Molecular biology studies are pioneers in parasitic research with the aim of discovering potential targets for drug development. Among them are the telomeres, DNA-protein structures that play an important role in the long term in cell cycle/survival. Telomeres are the physical ends of eukaryotic chromosomes. Due to their multiple interactions with different proteins that confer a likewise complex dynamic, they have emerged as objects of interest in many medical studies, including studies on leishmaniases. This review aims to gather information and elucidate what we know about the phenomena behind Leishmania spp. telomere maintenance and how it impacts the parasite's cell cycle.
Assuntos
Ciclo Celular , Leishmania/citologia , Leishmania/enzimologia , Telomerase/metabolismo , Telômero/metabolismo , Humanos , Modelos Biológicos , FilogeniaRESUMO
Bladder urothelial carcinoma (UC) it is the fifth most prevalent carcinoma in humans, nevertheless in children and young adults it's very rare. It usually occurs in older adults. Literature on UC in pediatric population is limited and important information (risk factors, follow-up protocols, etc.) are poorly defined. We present an 11-year-old boy with a painful macroscopic hematuria. Ultrasound revealed a heterogeneous intravesical mass without extravesical extension, which was confirmed by computed tomography (CT) and magnetic resonance imaging (MRI). The first biopsy was compatible with urothelial papilloma. After 1 year, he returned with a bigger mass. Transurethral resection of the bladder (TURB) was performed and immunohistochemistry showed low-grade papillary UC with a high-grade component, with tumor free margin. Tumor had mutations in the BRAF and KRAS genes. Two and a half years after the resection the patient has no recurrence. Less than 1% of bladder UC occur in the first two decades of life. Gross hematuria is a common symptom. Ultrasound is generally the first diagnostic tool. MRI is also helpful, but cystoscopy allows definitive diagnosis. Transurethral resection of the bladder (TURB) is the standard treatment, with good results and low recurrence rate, and it was the treatment of choice for our patient, that remains free of disease. The BRAF and KRAS gene mutations were never described before in pediatric UC. There are only few cases in literature of pediatric UC that present a tumor genetic profile; therefore, our case report adds more information to this very rare disease in children.
RESUMO
INTRODUCTION: Acute kidney injury (AKI) is common in acute myocardial infarction (AMI) patients and has serious prognostic implications. The early identification of patients at risk of developing AKI at the emergency department (ED) can reduce its incidence. METHODS: Patients with ST-segment elevation myocardial infarction (STEMI) at the ED were included. Associated factors playing a role at ED presentation and during hospitalization were collected, and independent risk factors of developing AKI were assessed. RESULTS: Mean age among patients (n = 406, 69.7% male) was 62.5 ± 12.5 years. At ED admission, the mean glomerular filtration rate (GFR) was 70.5 ± 28.1 mL/min per 1.73 m(2), and 140 (34.5%) patients had a GFR <60 mL/min per 1.73 m(2). Eighty-three patients (20.4%) developed AKI: 47 (11.6%) with stage 1, 26 (6.4%) with stage 2 and 10 (2.5%) with stage 3. Mortality was 11.8% and was higher in patients with AKI (34.9% vs 5.9%, P < .0001). Univariate analysis disclosed age, reduced GFR at presentation, severe Killip class, heart rate and longer door-to-needle time as risk factors to develop AKI. Moreover, these patients received less ß-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the ED. Multivariate analysis revealed that age, Killip class, heart rate, door-to-needle time, and ß-blocker non-use were independent factors associated with AKI. These factors provided the ED physician with good accuracy in identifying patients at high risk of developing AKI. CONCLUSION: Factors associated with AKI in STEMI patients allowed physicians to identify patients at high risk in the ED. Moreover, reduced door-to-needle time and ß-blocker use were associated with renal protection in AMI patients.