Acute effects of cigarette smoking in habitual smokers, a focus on endothelial function

AbstractBackgroundThe chronic effect of cigarette (cig.) smoking is well established. The acute effect of smoking abolishes the concept, argued by heavy smokers, to decrease the number of smoked cigarettes instead of quitting.AimTo detect the acute effects of cigarette smoking and the duration of these effects.Patients and methodsThirty four smokers (age 21–35years) were studied at 3 occasions; 9h after the last cig. smoking, 5min after one cig. smoking and 30min after 3 cig. smoking within 30min. They were subjected to measurement of both ventricular functions using standard and tissue Doppler imaging (TDI), aortic distensibility, stiffness and endothelial function assessment by endothelium-dependent flow-mediated dilatation (FMD) and maximum vasodilatation.ResultsAfter one cigarette smoking, we found a statistically significant effect on blood pressure, Heart Rate, FMD percent, Dilation Ratio, aortic distensibility (P=0.007), and aortic stiffness index (ASI) (P=0.01). Furthermore the LV diastolic function was significantly impaired after smoking. Despite disappearance of acute effect of 3 cig. smoking within 30min on blood pressure, Heart Rate and aortic distensibility, a significant difference was still found as regards FMD percent and dilation ratio denoting the extension of the endothelial dysfunction for more than 30min after the last cigarette.ConclusionMany acute changes occur following one cigarette smoking even in habitual smokers. Persistence of endothelial dysfunction parameters after smoking indicates the failure of circulation adaptation in response to such offense that might contribute to the precipitation of acute events in vulnerable patients

Legendre-Gauss-Lobatto collocation method for solving multi-dimensional systems of mixed Volterra-Fredholm integral equations

Integral equations play a crucial role in many scientific and engineering problems, though solving them is often challenging. This paper addresses the solution of multi-dimensional systems of mixed Volterra-Fredholm integral equations (SMVF-IEs) by means of a Legendre-Gauss-Lobatto collocation method. The one-dimensional case is addressed first. Afterwards, the method is extended to two-dimensional linear and nonlinear SMVF-IEs. Several numerical examples reveal the effectiveness of the approach and show its superiority in comparison to other alternative techniques for treating SMVF-IEs

Value of diffusion MRI versus [18F]FDG PET/CT in detection of cervical nodal metastases in differentiated thyroid cancer patients

Background: In differentiated thyroid cancer (DTC) patients, cervical nodal metastasis is a negative prognostic factor. Preoperative imaging plays an important role in treatment planning for nodal metastasis and recurrence. The aim of the study is to compare the diagnostic performance of the diffusion-weighted magnetic resonance imaging (DW-MRI) and the F-18 flurodeoxyglucose positron emission computed tomography ([18F]FDG PET/CT) in detection of cervical nodal deposits in DTC patients. Materal and methods: The study was conducted on 30 patients, each performed both modalities just before the surgery. The gold standard was the pathological specimens with post-operative clinico-radiological follow-up, to assess the diagnostic performance of each modality. Results: Based on pathological and post-operative clinico-radiological follow up data. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were 84%, 80%, 50%, 95% and 83% for PET/CT compared to 84%, 60%, 42.8%, 91.3% and 80% for DW-MRI. On comparing the diagnostic performance of combined DW-MRI and PET/CT to each modality alone, the sensitivity and NPV were improved to 96% and 80% respectively. Conclusions: [18F]FDG PET/CT study is a valuable diagnostic modality for the assessment of cervical nodal deposits in DTC patients, surpassing DW-MRI. Combined PET/CT and DW-MRI techniques seemed to have synergistic performance, mainly in terms of sensitivity and NPV, for detection of nodal metastases

Role of CT enterography in assessment of Crohn's disease activity: Correlation with histopathologic diagnosis

AbstractAimTo evaluate the radiological signs of gastro-intestinal inflammation at CT enterography and to assess its accuracy in determining the degree of activity in patients with Crohn's disease (CD).MethodsCT enterography was performed in 26 CD patients and evaluated for the following parameters: mucosal enhancement, abnormal wall thickening, engorged vasa recta, increased density of the mesenteric fat and enlarged mesenteric lymph nodes. Correlations between CT findings and histopathologic results were made using McNemar test.ResultsThere was no significant statistical difference in mucosal enhancement and wall thickening between moderate and severe disease (P=0.631 and 0.138, respectively) whereas engorged vasa recta, fat edema and lymph node enlargement had successfully discriminated between moderate and severe histological findings (P=0.009, <0.001 and 0.045, respectively). Moderate disease was diagnosed correctly by CTE in 50% of cases while severe disease was diagnosed in 100% of cases. When we reconditioned the presence of two CTE severity criteria to diagnose severe disease, the sensitivity to predict moderate disease activity increased to 80%.ConclusionCT enterography is a sensitive and specific non-invasive imaging modality for evaluating the degree of activity of Crohn's disease, and should be considered in its diagnostic and management algorithms

Genomic instability in human cancer: molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology

Management of Extremity Venous Thrombosis in Neonates and Infants: An Experience From a Resource Challenged Setting

We aimed to evaluate the outcome of different treatment modalities for extremity venous thrombosis (VT) in neonates and infants, highlighting the current debate on their best tool of management. This retrospective study took place over a 9-year period from January 2009 to December 2017. All treated patients were referred to the vascular and pediatric surgery departments from the neonatal intensive care unit. All patients underwent a thorough history-taking as well as general clinical and local examination of the affected limb. Patients were divided into 2 groups: group I included those who underwent a conservative treated with the sole administration of unfractionated heparin (UFH), whereas group II included those who were treated with UFH plus warfarin. Sixty-three patients were included in this study. They were 36 males and 27 females. Their age ranged from 3 to 302 days. Forty-one (65%) patients had VT in the upper limb, whereas the remaining 22 (35%) had lower extremity VT. The success rate of the nonsurgical treatment was accomplished in 81% of patients. The remaining 19% underwent limb severing, due to established gangrene. The Kaplan-Meier survival method revealed a highly significant increase in both mean and median survival times in those groups treated with heparin and warfarin compared to heparin-only group (P < .001). Nonoperative treatment with anticoagulation or observation (ie, wait-and-see policy) alone may be an easily applicable, effective, and a safe modality for management of VT in neonates and infants, especially in developing countries with poor or highly challenged resource settings

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression