The effect of long term nicotine exposure on endothelial function in rats

WOS: 000588164100001PubMed: 33172288Nicotine is one of the main chemicals in the cigarettes responsible for addiction formation. Many researches investigating the effects of nicotine on coronary heart disease and atherosclerosis have been published. the robustness of endothelial cells is very important in the development of atherosclerosis. the aim of this study is to evaluate the effect of nicotine exposure on the indicators of endothelial function either by examining the vascular reactivity of aorta taken from rats exposed to nicotine during prenatal (starting by the mating period) and postnatal periods (6 weeks after delivery), or by determining the protein expression of nitric oxide synthase (NOS) enzymes, NADPH oxidase (Nox) and nitrotyrosine. Chronic nicotine exposure at 6 mg/L in drinking water produced a significant decrease in phenylephrine contractility of thoracic aortic rings compared to control and low dose exposure group (0.4 mg/L, p < 0.001). Endothelium-dependent relaxations to acetylcholine increased dose-dependently while no changes were observed in endothelium-independent relaxations to sodium nitroprusside and protein expressions in rat thoracic aorta. It has been concluded that long term nicotine exposure does not have serious effects on endothelial vasodilator response directly and does not change protein expression of NOS or Nox enzymes. However, more studies should be done for the exact mechanisms responsible for the effect of nicotine on endothelial function.Ege University Scientific Research Projects FundingEge University [09-TIP-020]The study was supported by Ege University Scientific Research Projects Funding [Project no: 09-TIP-020]

Erythropoietin attenuates neuronal injury and potentiates the expression of pCREB in anterior horn after transient spinal cord ischemia in rats

Background: Recent studies have suggested that EPO activates the CREB transcription pathway and increases BDNF expression and production, which contributes to EPO-mediated neuroprotection. We investigated whether EPO has a neuroprotective effect against ISCI in rats and examined the involvement of CREB protein phosphorylation in this process

Prognostic Impact of Histologic Subtype in Non-Small Cell Lung Cancer Patients Treated with Gamma Knife Radiosurgery: Retrospective Analysis of 104 Patients

AIM: In this study, factors affecting survival, local failure, distant brain failure, whole brain failure and whole-brain radiation therapy (WBRT) free survival according to histological subtypes were investigated in patients with brain metastases from non-small cell lung cancer (NSCLC). MATERIAL and METHODS: Patients with positive pathology reports for adenocarcinoma (ACA) and squamous cell carcinoma (SCC) were included in the study. Seventy-eight ACA and 26 SCC patients were included in the study. Patients with previous history of cerebral metastasis surgery and WBRT were excluded from the study. RESULTS: The median survival was calculated as 12.6 months for patients with ACA and 5.9 months for patients with SCC. One-year distant brain failure was calculated as 65.1% in ACA patients and 39.6% in SCC patients. One-year whole brain failure was calculated as 58.1% in ACA patients and 39.6% in SCC patients. The one-year freedom from WBRT rate was calculated as 72.8% in ACA patients and 56.3% in SCC patients. SCC histology was considered as a significant factor in deterioration of overall survival in multivariate analysis. SCC histology, the increase in the number of metastases and RPA class were factors that caused an increase in distant brain failure. Also, SCC histology, the increase in the number of metastases and RPA class were factors that caused an increase in whole brain failure. CONCLUSION: SCC histology may be an important prognostic factor for overall survival. Also, due to high distant brain failure rate in SCC histology, WBRT can be added to treatment early

Frontline Nilotinib Treatment In Turkish Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia In Chronic Phase: Updated Results With 2 Years Of Follow-Up

Objectives: This report presents final results (24 months of follow-up) from the first prospective, national study of frontline nilotinib in chronic myeloid leukemia (CML) patients in Turkey. Methods: Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N = 112) received nilotinib 300 mg twice daily. The primary endpoint, which was the cumulative rate of major molecular response (MMR; BCR-ABL1 <= 0.1% on the International Scale [BCR-ABL1(IS)]) by 12 months, was previously reported (66.1% [80% CI, 59.7%-72.0%]). ClinicalTrials.gov identifier NCT01274351 Results: By 24 months, 83.0% of patients achieved MMR, and 50.9% achieved MR4.5 (BCR-ABL1(IS) <= 0.0032%). Safety results at 24 months were consistent with those at 12 months. No additional deaths or disease progressions to accelerated phase/blast crisis were observed between 12 and 24 months. Discussion: Treatment with nilotinib 300 mg twice daily for 2 years provided high MMR with a good safety/tolerability profile in newly diagnosed CML-CP patients in Turkey. Assessment of MMR across time points showed increasing rates through 18 months, after which as lower rate of increase was observed. The safety profile of nilotinib 300 mg twice daily with 24 months of follow-up was similar to that observed at 12 months, and no new safety concerns were identified. These efficacy and safety findings are consistent with the results from the 12-month analysis of this study and from previous nilotinib studies. These findings support nilotinib as an option for frontline treatment of CML-CP. Conclusion: Frontline nilotinib treatment provided sustained efficacy, with good tolerability, over 24 months in newly diagnosed CML-CP patients.WoSScopu

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase

WOS: 000384401200003PubMed ID: 27501474Objective: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL10.1% on the International Scale [BCR-ABL1(IS)]) by 12months.Methods: Patients with newly diagnosed CML-CP were treated with nilotinib 300mg twice daily. This analysis was based on the first 12months of follow-up in a 24-month study.Results and Conclusions: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1(IS) 0.0032%) by 12months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP.Novartis Pharmaceuticals CorporationNovartisThis study was funded by Novartis Pharmaceuticals Corporation