Anger is associated with subclinical atherosclerosis in low SES but not in higher SES men and women

We investigated the associations of anger and cynicism with carotid artery intima-media thickness (IMT) and whether these associations were moderated by childhood or adulthood socioeconomic status (SES). The participants were 647 men and 893 women derived from the population-based Cardiovascular Risk in Young Finns Study. Childhood SES was measured in 1980 when the participants were aged 3-18. In 2001, adulthood SES, anger, cynicism, and IMT were measured. There were no associations between anger or cynicism and IMT in the entire population, but anger was associated with thicker IMT in participants who had experienced low SES in childhood. This association persisted after adjustment for a host of cardiovascular risk factors. It is concluded that the ill health-effects of psychological factors such as anger may be more pronounced in individuals who have been exposed to adverse socioeconomic circumstances early in life.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

Ruismallasuute vähägluteenisessa kauraleivonnassa

Tutkielman kirjallisuuskatsauksessa tarkasteltiin kauran leivontateknologisia ominaisuuksia, entsyymiaktiivista leivontaa ja ruismaltaan hyödyntämistä vähägluteenisessa leivonnassa. Kokeellisessa osiossa tutkittiin ruismallashapantaikinasta valmistetun uutteen vaikutusta kaurataikinan viskositeettiin ja kauraleivän ominaisuuksiin. Työn tarkoituksena oli kehittää maultaan ja rakenteeltaan onnistunut rukiinmakuinen kauraleipä. Ruismaltaan entsyymien annettiin pilkkoa keliaakikolle haitallisia rukiin prolamiineja hapantaikinaprosessissa. Hapantaikinasta erotettiin uute sentrifugoimalla. Leivontakokeisiin käytettiin entsyymiaktiivista ja kuumentamalla inaktivoitua uutetta. Uutteella korvattiin taikinavettä 15, 25 ja 30 % (taikinan painosta). Leivonta toteutettiin miniatyyrikoossa, vuokaleivontana 20 g:n taikinapaloja käyttäen. Taikinoiden viskositeetti mitattiin tarkoituksena seurata beetaglukaanin hydrolyysiä. Rukiin makua mitattiin koulutetun raadin avulla. Happaman uutteen lisäys laski taikinan pH-arvoa noin 5,8:sta noin 4,4:ään. Entsyymiaktiivisen uutteen lisäys laski taikinan viskositeettia ja inaktivoitu uute puolestaan kasvatti sitä. Leipien sisus tiivistyi, jolloin mitatut sisuksen kovuudet kasvoivat uutteen lisäyksen myötä. Uutelisäys paransi leipien makua ja aromia. Uutteen vaikutuksesta leipien huokoset olivat pienempiä ja ne jakaantuivat tasaisemmin leipämatriisiin. Jos uutetta käytettiin inaktivoituna, leipien murenevuus kasvoi. Tutkimuksessa kehitetyn teknologian avulla oli mahdollista valmistaa hyvänlaatuinen, rukiinmakuinen kauraleipä myös ilman että uutteen entsyymit inaktivoitiin keittämällä. Tähän vaikutti ilmeisesti taikinan alhainen pH, joka inhiboi alfa-amylaasia, ja kauratärkkelyksen korkea liisteröitymislämpötila, jolloin entsyymien inaktivoituminen paiston aikana tapahtui ennen kuin tärkkelys tuli alttiiksi liialliselle pilkkoutumiselle. Tämä mahdollistaa uutteen käytön osana leivontaprosessia ilman inaktivointia. Hapantaikinafermentaatio osana gluteenitonta leivontaa havaittiin toimivaksi yhdistelmäksi, sillä se paransi leivän väriä, makua ja rakennetta. Myös leivän homeeton aika parani jo vähäisenkin uutelisäyksen vaikutuksesta. Näyttää siltä, että tämän teknologian avulla on mahdollista tuoda esille pitkään kaivattua rukiin makua vähägluteenisten kauraleipien valikoimassa. Laskennallisesti ja aiempiin tuloksiin tukeutuen, voitiin päätellä, että leivän prolamiinipitoisuudessa on mahdollista päästä tasolle 63,5 mg/kg, mutta jatkokehityksen avulla päästäisiin luultavasti vielä parempiin tuloksiin.

High-risk patients and high-risk grafts in infrainguinal bypass for critical limb ischaemia

The main purpose of revascularization procedures for critical limb ischaemia (CLI) is to preserve the leg and sustain the patient s ambulatory status. Other goals are ischaemic pain relief and healing of ischaemic ulcers. Patients with CLI are usually old and have several comorbidities affecting the outcome. Revascularization for CLI is meaningless unless both life and limb are preserved. Therefore, the knowledge of both patient- and bypass-related risk factors is of paramount importance in clinical decision-making, patient selection and resource allocation. The aim of this study was to identify patient- and graft-related predictors of impaired outcome after infrainguinal bypass for CLI. The purpose was to assess the outcome of high-risk patients undergoing infrainguinal bypass and to evaluate the usefulness of specific risk scoring methods. The results of bypasses in the absence of optimal vein graft material were also evaluated, and the feasibility of the new method of scaffolding suboptimal vein grafts was assessed. The results of this study showed that renal insufficiency - not only renal failure but also moderate impairment in renal function - seems to be a significant risk factor for both limb loss and death after infrainguinal bypass in patients with CLI. Low estimated GFR (PIENEMPI KUIN 30 ml/min/1.73 m2) is a strong independent marker of poor prognosis. Furthermore, estimated GFR is a more accurate predictor of survival and leg salvage after infrainguinal bypass in CLI patients than serum creatinine level alone. We also found out that the life expectancy of octogenarians with CLI is short. In this patient group endovascular revascularization is associated with a better outcome than bypass in terms of survival, leg salvage and amputation-free survival especially in presence of coronary artery disease. This study was the first one to demonstrate that Finnvasc and modified Prevent III risk scoring methods both predict the long-term outcome of patients undergoing both surgical and endovascular infrainguinal revascularization for CLI. Both risk scoring methods are easy to use and might be helpful in clinical practice as an aid in preoperative patient selection and decision-making. Similarly than in previous studies, we found out that a single-segment great saphenous vein graft is superior to any other autologous vein graft in terms of mid-term patency and leg salvage. However, if optimal vein graft is lacking, arm vein conduits are superior to prosthetic grafts especially in infrapopliteal bypasses for CLI. We studied also the new method of scaffolding suboptimal quality vein grafts and found out that this method may enable the use of vein grafts of compromised quality otherwise unsuitable for bypass grafting. The remarkable finding was that patients with the combination of high operative risk due to severe comorbidities and risk graft have extremely poor survival, suggesting that only relatively fit patients should undergo complex bypasses with risk grafts. The results of this study can be used in clinical practice as an aid in preoperative patient selection and decision-making. In the future, the need of vascular surgery will increase significantly as the elderly and diabetic population increases, which emphasises the importance of focusing on those patients that will gain benefit from infrainguinal bypass. Therefore, the individual risk of the patient, ambulatory status, outcome expectations, the risk of bypass procedure as well as technical factors such as the suitability of outflow anatomy and the available vein material should all be assessed and taken into consideration when deciding on the best revascularization strategy.

Influence of cerebral ischemia and post-ischemic reperfusion on mitochondrial oxidative phosphorylation

Unilateral ischemia in the right cerebral hemisphere of the rat was induced by ligation of the right common carotid artery coupled with controlled hemorrhage to produce hypotension (25±8 mm/Hg). Where indicated after 30 min of ischemia, the withdrawn blood was reinfused to restore arterial pressure to normal. Mitochondria isolated from the ipsilateral hemisphere after 30 min of ischemia showed significantly lower respiratory rates than the organelles isolated from the contralateral side. Oxidation of NAD+-linked substrates was more sensitive to inhibition in ischemia (30%) than was of ferrocytochromec (12%), succinate oxidation being intermediate. The activities of membrane-bound dehydrogenases (both NADH and succinate-linked) were also significantly lowered. Ischemia did not affect the cytochrome content of mitochondria. Respiratory activity (NAD+-linked) of mitochondria isolated from the ipsilateral hemisphere was twice as sensitive to inhibition by fatty acid as was of preparations from the contralateral side. Mitochondria isolated from cerebral cortex after 90 min of post-ischemic reperfusion showed no significant improvement in the rate of substrate oxidation. Adenine nucleotide translocase activity and energy-dependent Ca2+ uptake, both of which decreased significantly in mitochondria isolated from the ischemic brain, showed little recovery, on reperfusion. These observations suggested the strong possibility that the deleterious effects of ischemia on mitochondrial respiratory function might be mediated by free fatty acids that are known to accumulate in large amounts in ischemic tissues. The pattern of inhibition of ATPase activity was consistent with this view.

Myoblast Sheet Transplantation for Treatment of Heart Failure after Myocardial Infarction

Heart failure is a common, severe, and progressive condition associated with high mortality and morbidity. Because of population-aging in the coming decades, heart failure is estimated to reach epidemic proportions. Current medical and surgical treatments have reduced mortality, but the prognosis for patients has remained poor. Transplantation of skeletal myoblasts has raised hope of regenerating the failing heart and compensating for lost cardiac contractile tissue. In the present work, we studied epicardial transplantation of tissue-engineered myoblast sheets for treatment of heart failure. We employed a rat model of myocardial infarction-induced acute and chronic heart failure by left anterior descending coronary artery ligation. We then transplanted myoblast sheets genetically modified to resist cell death after transplantation by expressing antiapoptotic gene bcl2. In addition, we evaluated the regenerative capacity of myoblast sheets expressing the cardioprotective cytokine hepatocyte growth factor in a rat chronic heart failure model. Furthermore, we utilized in vitro cardiomyocyte and endothelial cell culture models as well as microarray gene expression analysis to elucidate molecular mechanisms mediating the therapeutic effects of myoblast sheet transplantation. Our results demonstrate that Bcl2-expression prolonged myoblast sheet survival in rat hearts after transplantation and induced secretion of cardioprotective, proangiogenic cytokines. After acute myocardial infarction, these sheets attenuated left ventricular dysfunction and myocardial damage, and they induced therapeutic angiogenesis. In the chronic heart failure model, inhibition of graft apoptosis by Bcl-2 improved cardiac function, supported survival of cardiomyocytes in the infarcted area, and induced angiogenesis in a vascular endothelial growth factor receptor 1- and 2-dependent mechanism. Hepatocyte growth factor-secreting myoblast sheets further enhanced the angiogenic efficacy of myoblast sheet therapy. Moreover, myoblast-secreted paracrine factors protected cardiomyocytes against oxidative stress in an epidermal growth factor receptor- and c-Met dependent manner. This protection was associated with induction of antioxidative genes and activation of the unfolded protein response. Our results provide evidence that inhibiting myoblast sheet apoptosis can enhance the sheets efficacy for treating heart failure after acute and chronic myocardial infarction. Furthermore, we show that myoblast sheets can serve as vehicles for delivery of growth factors, and induce therapeutic angiogenesis in the chronically ischemic heart. Finally, myoblasts induce, in a paracine manner, a cardiomyocyte-protective response against oxidative stress. Our study elucidates novel mechanisms of myoblast transplantation therapy, and suggests effective means to improve this therapy for the benefit of the heart failure patient.

Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.

Dynamics of pulsed flow in an elastic tube

Internal haemorrhage, often leading to cardio-vascular arrest happens to be one of the prime sources of high fatality rates in mammals. We propose a simplistic model of fluid flow in our attempt to specify the location of the haemorrhagic spot, which, if located accurately, could possibly be operated leading to an instant cure. The model we employ for the purpose is basically fluid mechanical in origin and consists of a viscous fluid, pumped by a periodic force and flowing through an elastic tube. The analogy is with that of blood, pumped from the heart and flowing through an artery or vein. Our results, aided by graphical illustrations, match reasonably well with experimental observations.

Cerebroprotective activity of Wedelia calendulacea on global cerebral ischemia in rats

The present study was to investigate the effect of W. calendulacea on ischemia and reperfusion-induced cerebral injury. Cerebral ischemia was induced by occluding right and left common carotid arteries (global cerebral ischemia) for 30 min followed by reperfusion for 1 h and 4 h individually. Various biochemical alterations, produced subsequent to the application of bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO), hydrogen peroxide (H(2)O(2)), and decrease in reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), level in the brain tissue, Western blot analysis (Cu-Zn-SOD and CAT) and assessment of cerebral infarct size were measured. All those enzymes are markedly reversed and restored to near normal level in the groups pre-treated with W. calendulacea (250 and 500 mg/kg given orally in single and double dose/day for 10 days) in dose-dependent way. The effect of W. calendulacea had increased significantly the protein expression of copper/zinc superoxide dismutase (Cu-Zn-SOD) and CAT in cerebral ischemia. W. claendulacea was markedly decrease cerebral infarct damages but results are not statistically significant. It can be concluded that W. calendulacea possesses a neuroprotective activity against cerebral ischemia in rat.

Pulse transit time differential measurement by fiber Bragg grating pulse recorder

The present study reports a noninvasive technique for the measurement of the pulse transit time differential (PTTD) from the pulse pressure waveforms obtained at the carotid artery and radial artery using fiber Bragg grating pulse recorders (FBGPR). PTTD is defined as the time difference between the arrivals of a pulse pressure waveform at the carotid and radial arterial sites. The PTTD is investigated as an indicator of variation in the systolic blood pressure. The results are validated against blood pressure variation obtained from a Mindray Patient Monitor. Furthermore, the pulse wave velocity computed from the obtained PTTD is compared with the pulse wave velocity obtained from the color Doppler ultrasound system and is found to be in good agreement. The major advantage of the PTTD measurement via FBGPRs is that the data acquisition system employed can simultaneously acquire pulse pressure waveforms from both FBGPRs placed at carotid and radial arterial sites with a single time scale, which eliminates time synchronization complexity. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

Analysis of Wrist Pulse Signals Using Spatial Features in Time Domain

Wrist pulse signal contains more important information about the health status of a person and pulse signal diagnosis has been employed in oriental medicine since very long time. In this paper we have used signal processing techniques to extract information from wrist pulse signals. For this purpose we have acquired radial artery pulse signals at wrist position noninvasively for different cases of interest. The wrist pulse waveforms have been analyzed using spatial features. Results have been obtained for the case of wrist pulse signals recorded for several subjects before exercise and after exercise. It is shown that the spatial features show statistically significant changes for the two cases and hence they are effective in distinguishing the changes taking place due to exercise. Support vector machine classifier is used to classify between the groups, and a high classification accuracy of 99.71% is achieved. Thus this paper demonstrates the utility of the spatial features in studying wrist pulse signals obtained under various recording conditions. The ability of the model to distinguish changes occurring under two different recording conditions can be potentially used for health care applications.

Study of wrist pulse signals using time domain spatial features

Blood travels throughout the body and thus its flow is modulated by changes in body condition. As a consequence, the wrist pulse signal contains important information about the status of the human body. In this work we have employed signal processing techniques to extract important information from these signals. Radial artery pulse pressure signals are acquired at wrist position noninvasively for several subjects for two cases of interest, viz. before and after exercise, and before and after lunch. Further analysis is performed by fitting a bi-modal Gaussian model to the data and extracting spatial features from the fit. The spatial features show statistically significant (p < 0.001) changes between the groups for both the cases, which indicates that they are effective in distinguishing the changes taking place due to exercise or food intake. Recursive cluster elimination based support vector machine classifier is used to classify between the groups. A high classification accuracy of 99.71% is achieved for the exercise case and 99.94% is achieved for the lunch case. This paper demonstrates the utility of certain spatial features in studying wrist pulse signals obtained under various experimental conditions. The ability of the spatial features in distinguishing changing body conditions can be potentially used for various healthcare applications. (C) 2015 Elsevier Ltd. All rights reserved.

Accuracy in Copy Number Calling by qPCR and PRT : A Matter of DNA

7 p.

Experimental and theoretical studies of Notch signaling-mediated spatial pattern

Notch signaling acts in many diverse developmental spatial patterning processes. To better understand why this particular pathway is employed where it is and how downstream feedbacks interact with the signaling system to drive patterning, we have pursued three aims: (i) to quantitatively measure the Notch system's signal input/output (I/O) relationship in cell culture, (ii) to use the quantitative I/O relationship to computationally predict patterning outcomes of downstream feedbacks, and (iii) to reconstitute a Notch-mediated lateral induction feedback (in which Notch signaling upregulates the expression of Delta) in cell culture. The quantitative Notch I/O relationship revealed that in addition to the trans-activation between Notch and Delta on neighboring cells there is also a strong, mutual cis-inactivation between Notch and Delta on the same cell. This feature tends to amplify small differences between cells. Incorporating our improved understanding of the signaling system into simulations of different types of downstream feedbacks and boundary conditions lent us several insights into their function. The Notch system converts a shallow gradient of Delta expression into a sharp band of Notch signaling without any sort of feedback at all, in a system motivated by the Drosophila wing vein. It also improves the robustness of lateral inhibition patterning, where signal downregulates ligand expression, by removing the requirement for explicit cooperativity in the feedback and permitting an exceptionally simple mechanism for the pattern. When coupled to a downstream lateral induction feedback, the Notch system supports the propagation of a signaling front across a tissue to convert a large area from one state to another with only a local source of initial stimulation. It is also capable of converting a slowly-varying gradient in parameters into a sharp delineation between high- and low-ligand populations of cells, a pattern reminiscent of smooth muscle specification around artery walls. Finally, by implementing a version of the lateral induction feedback architecture modified with the addition of an autoregulatory positive feedback loop, we were able to generate cells that produce enough cis ligand when stimulated by trans ligand to themselves transmit signal to neighboring cells, which is the hallmark of lateral induction.

Designing conformational control of human tissue transglutaminase

Understanding the mechanisms of enzymes is crucial for our understanding of their role in biology and for designing methods to perturb or harness their activities for medical treatments, industrial processes, or biological engineering. One aspect of enzymes that makes them difficult to fully understand is that they are in constant motion, and these motions and the conformations adopted throughout these transitions often play a role in their function.

Traditionally, it has been difficult to isolate a protein in a particular conformation to determine what role each form plays in the reaction or biology of that enzyme. A new technology, computational protein design, makes the isolation of various conformations possible, and therefore is an extremely powerful tool in enabling a fuller understanding of the role a protein conformation plays in various biological processes.

One such protein that undergoes large structural shifts during different activities is human type II transglutaminase (TG2). TG2 is an enzyme that exists in two dramatically different conformational states: (1) an open, extended form, which is adopted upon the binding of calcium, and (2) a closed, compact form, which is adopted upon the binding of GTP or GDP. TG2 possess two separate active sites, each with a radically different activity. This open, calcium-bound form of TG2 is believed to act as a transglutaminse, where it catalyzes the formation of an isopeptide bond between the sidechain of a peptide-bound glutamine and a primary amine. The closed, GTP-bound conformation is believed to act as a GTPase. TG2 is also implicated in a variety of biological and pathological processes.

To better understand the effects of TG2’s conformations on its activities and pathological processes, we set out to design variants of TG2 isolated in either the closed or open conformations. We were able to design open-locked and closed-biased TG2 variants, and use these designs to unseat the current understanding of the activities and their concurrent conformations of TG2 and explore each conformation’s role in celiac disease models. This work also enabled us to help explain older confusing results in regards to this enzyme and its activities. The new model for TG2 activity has immense implications for our understanding of its functional capabilities in various environments, and for our ability to understand which conformations need to be inhibited in the design of new drugs for diseases in which TG2’s activities are believed to elicit pathological effects.