35 research outputs found

    The type I insulin-like growth factor regulates the liver stromal response to metastatic colon carcinoma cells.

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    Hepatic stellate cells (HSC) play a major role in initiating the liver fibrogenic (wounding) response of the liver and can also orchestrate a pro-metastatic microenvironment in the liver in response to invading cancer cells. Here we explored the role of the hepatic stellate cells in colon carcinoma liver metastasis with emphasis on the contribution of the insulin-like growth factor (IGF) axis to their activation and function. To this end, we used mice with a Tamoxifen inducible liver IGF-I deficiency. We found that in mice with a sustained IGF-I deficiency, recruitment and activation of HSC into tumor-infiltrated areas of the liver were markedly diminished, resulting in decreased collagen deposition and reduced tumor expansion. In addition, IGF-I could rescue HSC from apoptosis induced by pro-inflammatory factors such as TNF-α known to be upregulated in the early stages of liver metastasis. Moreover, in surgical specimens, activated IGF-IR was observed on HSC-like stromal cells surrounding colorectal carcinoma liver metastases. Finally, IGF-targeting in vivo using an IGF-Trap caused a significant reduction in HSC activation in response to metastatic colon cancer cells. Therefore, our data identify IGF as a survival factor for HSC and thereby, a promoter of the pro-metastatic microenvironment in the liver. IGF-targeting could therefore provide a strategy for curtailing the pro-metastatic host response of the liver during the early stages of liver metastasis

    Framework for parametric assessment of operational and embodied energy impacts utilising BIM

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    In recent years advances in digital tools have been leading the way in the construction of cleaner, more energy-efficient buildings. Furthermore, improvements in Building Information Modelling (BIM) have resulted in various tools being used to assess building performance and overall Life Cycle Analysis (LCA). This work offers a unique insight into the development of a parametric LCA BIM tool, focusing on both operational and embodied energy perspectives through case study analysis of a commercial and a domestic building in the UK. A mixed research method was employed combining a literature review, qualitative and quantitative LCA case study analysis, and parametric modelling. The results indicate that embodied energy is much more critical in the early stages of the building's life, then is quickly overtaken by operational energy. In addition, many variations exist in energy outputs between domestic and commercial buildings. Operational energy takes a significant share in domestic buildings compared to commercial buildings. These variations are attributed to different design methods, construction materials, occupancy patterns and energy demands. The study proposes an LCA-BIM interactive user-led method of addressing energy hotspots for both operational and embodied elements, which can provide more instant identification of energy critical areas. Such an approach can offer real alternative BIM-based analysis tools during the design stages, compared to those currently being used, which focus mainly on either LCA of operational or embodied energy

    Peroxynitrite induced decrease in Na+, K+-ATPase activity is restored by taurine

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    AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In the present study, the effect of taurine on changes of liver plasma membrane Na+, K+-ATPase induced by ONOO- was investigated

    Homocysteine and pro-inflammatory cytokine concentrations in acute heart disease

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    Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease. (C) 2010 Elsevier Ltd. All rights reserved

    Wpływ sedacji w trakcie echokardiografii przezprzełykowej na zmienność rytmu serca: porównanie sedacji za pomocą hipnozy z sedacją farmakologiczną

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    Background: There is no ideal sedation technique that can be used during transoesophageal echocardiography (TEE), and the data concerning the effects of available sedation techniques on heart rate variability (HRV) are limited. Aim: To compare the effects of sedation through hypnotherapy with medical sedation achieved by midazolam on HRV. Methods: We recruited 76 patients with an indication of TEE; the age range was 18–83 years. In Group T there were 26 patients who had the procedure under topical pharyngeal anaesthesia, in Group D there were 23 patients who received midazolam, and in Group H there were 27 patients receiving hypnosis. All patients had an IV access; throughout the procedure heart rate, rhythm electrocardiography, and peripheric O2 saturation were monitored with a non-invasive monitor, and blood pressure measurements were taken every 3 min. Rhythm Holter recordings were obtained from all patients and TEE was performed. Results: When time domain parameters for HRV were compared in all three groups, the hypnosis group had significant increases in pNN50 and RMSSD compared to Groups D and T (p < 0.05). As concerns frequency domain parameters, there were no significant differences between groups where low frequency (LF) was decreased in hypnosis group and high frequency (HF) was increased (p > 0.05). However, LF/HF was decreased statistically significantly (p < 0.05) when compared with the midazolam group. Conclusions: Contrary to standard sedation in TEE patients, when hypnosis is used autonomic cardiac tone is modified to a significant extent. Hypnotic sedation achieves this by increasing the parasympathetic activity, decreasing the sympathetic activity, and changing the sympathovagal interaction balance.  Wstęp: Nie ma idealnej metody sedacji, która mogłaby być stosowana w trakcie echokardiografii przezprzełykowej (TEE), a dane dotyczące wpływu dostępnych metod sedacji na zmienność rytmu serca (HRV) są ograniczone. Cel: Badanie przeprowadzono w celu porównania wpływu na HRV sedacji uzyskanej metodą hipnoterapii i sedacji farmakologicznej z zastosowaniem midazolamu. Metody: Do badania włączono 76 chorych ze wskazaniami do wykonania TEE, w wieku 18–83 lat. Grupa T obejmowała 26 chorych, u których badanie wykonano po zastosowaniu miejscowego znieczulenia gardła, grupa D — 23 chorych, którym podano midazolam, a grupa H — 27 chorych, których poddano hipnozie. U wszystkich pacjentów zapewniono dostęp dożylny. Przez cały czas trwania badania monitorowano częstość rytmu serca, zapis elektrokardiograficzny i saturację tlenem krwi obwodowej metodą nieinwazyjną; pomiary ciśnienia tętniczego wykonywano co 3 minuty. U wszystkich pacjentów uzyskano zapis rytmu serca metodą Holtera i przeprowadzono TEE. Wyniki: Porównując parametry HRV uzyskane w trzech grupach, stwierdzono, że w grupie poddanej hipnozie wartości pNN50 i RMSSD były istotnie wyższe niż w grupach D i T (p < 0,05). Na podstawie oceny parametrów analizy częstotliwościowej nie wykazano istotnych różnic między osobami poddanymi hipnozie, u których stwierdzono zmniejszenie mocy widma w zakresie niskich częstotliwości (LF) i zwiększenie w zakresie wysokich częstotliwości (HF) (p > 0,05). Jednak zaobserwowano statystycznie istotną (p < 0,05) redukcję współczynnika LF/HF w porównaniu z grupą, której podano midazolam. Wnioski: W przeciwieństwie do standardowej metody sedacji u chorych poddanych TEE stosowanie hipnozy wiązało się z istotną zmianą napięcia autonomicznego układu nerwowego serca. Sedacja za pomocą hipnozy powodowała zwiększenie aktywności przywspółczulnej, zmniejszenie aktywności współczulnej i zmianę balansu interakcji między układem współczulnym a przywspółczulnym (nerw błędny)

    Role of emergency physician–performed ultrasound in the differential diagnosis of abdominal pain

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    Objectives: This prospective study was performed to evaluate the diagnostic accuracy of bedside point-of-care abdominal ultrasonography performed by emergency physician in patients with non-traumatic acute abdominal pain. Methods: The patients, who were admitted to emergency department due to abdominal pain, were included in this study. The emergency physician obtained a routine history, physical examination, blood draws, and ordered diagnostic imaging. After the initial clinical examinations, all the patients underwent ultrasonography for abdominal pathologies by emergency physician and radiologist, respectively. Point-of-care abdominal ultrasonography compared with abdominal ultrasonography performed by radiologist as the gold standard. Results: The study included 122 patients. Gallbladder and appendix pathologies were the most commonly detected in the abdominal ultrasonography. Compared with abdominal ultrasonography, point-of-care abdominal ultrasonography was found to have 89% sensitivity and 94% specificity in gallbladder pathologies; 91% sensitivity and 91% specificity in acute appendicitis; 79% sensitivity and 97% specificity in abdominal free fluid; 83% sensitivity and 96% specificity in ovarian pathologies. Compared to final diagnosis, preliminary diagnoses of emergency physicians were correct in 92 (75.4%) patients. Conclusion: This study showed that emergency physicians were successful in identifying abdominal organ pathologies with point-of-care abdominal ultrasonography after training. © The Author(s) 2018

    Influences of genetic variants in interleukin-15 gene and serum interleukin-15 levels on coronary heart disease.

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    Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHID. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHID. Further studies are needed to confirm our hypothesis. (C) 2009 Elsevier Ltd. All rights reserved
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