STZ-diabetic rat heart maintains developed tension amplitude by increasing sarcomere length and crossbridge density

New Findings: What is the central question of this study? In the papillary muscle from type I diabetic rats, does diabetes-associated altered ventricular function result from changes of acto-myosin interactions and are these modifications attributable to a possible sarcomere rearrangement? What is the main finding and its importance? For the first time, we showed that type-I diabetes altered sarcomeric ultrastructure, as seen by transmission electron microscopy, consistent with physiological parameters. The diabetic condition induced slower timing parameters, which is compatible with a diastolic dysfunction. At the sarcomeric level, augmented β-myosin heavy chain content and increased sarcomere length and crossbridges' number preserve myocardial stroke and could concur to maintain the ejection fraction. Abstract: We investigated whether diabetes-associated altered ventricular function, in a type I diabetes animal model, results from a modification of acto-myosin interactions, through the in vitro recording of left papillary muscle mechanical parameters and examination of sarcomere morphology by transmission electron microscopy (TEM). Experiments were performed on streptozotocin-induced diabetic and age-matched control female Wistar rats. Mechanical isometric and isotonic indexes and timing parameters were determined. Using Huxley's equations, we calculated mechanics, kinetics and energetics of myosin crossbridges. Sarcomere length and A-band length were measured on TEM images. Type I and III collagen and β-myosin heavy chain (MHC) expression were determined by immunoblotting. No variation in resting and developed tension or maximum extent of shortening was evident between groups, but diabetic rats showed lower maximum shortening velocity and prolonged timing parameters. Compared to controls, diabetics also displayed a higher number of crossbridges with lower unitary force. Moreover, no change in type I and III collagen was associated to diabetes, but pathological rats showed a two-fold enhancement of β-MHC content and longer sarcomeres and A-band, detected by ultrastructural morphometry. Overall, these data address whether a preserved systolic function accompanied by an altered diastolic phase results from a recruitment of super-relaxed myosin heads or the phosphorylation of the regulatory light chain site in myosin. Although the early signs of diabetic cardiomyopathy were well expressed, the striking finding of our study was that, in diabetics, sarcomere modification may be a possible compensatory mechanism that preserves systolic function

Prostate-specific antigen: An unfamiliar protein in the human salivary glands

Objectives: The presence of prostate-specific antigen (PSA) in saliva and salivary glands has been reported. Nevertheless, its release pathway in these glands remains to be elucidated. Here, we showed PSA subcellular distribution focusing on its plausible route in human salivary parenchyma. Materials and Methods: Sections of parotid and submandibular glands were subjected to the immunohistochemical demonstration of PSA by the streptavidin–biotin method revealed by alkaline phosphatase. Moreover, ultrathin sections were collected on nickel grids and processed for immunocytochemical analysis, to visualize the intracellular distribution pattern of PSA through the observation by transmission electron microscopy. Results: By immunohistochemistry, in both parotid and submandibular glands PSA expression was detected in serous secretory acini and striated ducts. By immunocytochemistry, immunoreactivity was retrieved in the cytoplasmic compartment of acinar and ductal cells, often associated with small cytoplasmic vesicles. PSA labeling appeared also on rough endoplasmic reticulum and in the acini's lumen. A negligible PSA labeling appeared in most of the secretory granules of both glands. Conclusions: Our findings clearly support that human parotid and submandibular glands are involved in PSA secretion. Moreover, based on the immunoreactivity pattern, its release in oral cavity would probably occur by minor regulated secretory or constitutive-like secretory pathways

The human major sublingual gland and its neuropeptidergic and nitrergic innervations

Background: What textbooks usually call the sublingual gland in humans is in reality a tissue mass of two types of salivary glands, the anteriorly located consisting of a cluster of minor sublingual glands and the posteriorly located major sublingual gland with its outlet via Bartholin's duct. Only recently, the adrenergic and cholinergic innervations of the major sublingual gland was reported, while information regarding the neuropeptidergic and nitrergic innervations is still lacking. Methods: Bioptic and autoptic specimens of the human major sublingual gland were examined by means of immunohistochemistry for the presence of vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)-, substance P (SP)-, calcitonin gene related-peptide (CGRP)-, and neuronal nitric oxide synthase (nNOS)-labeled neuronal structures. Results: As to the neuropeptidergic innervation of secretory cells (here in the form of mucous tubular and seromucous cells), the findings showed many VIP-containing nerves, few NPY- and SP-containing nerves and a lack of CGRP-labeled nerves. As to the neuropeptidergic innervation of vessels, the number of VIP-containing nerves was modest, while, of the other neuropeptide-containing nerves under study, only few (SP and CGRP) to very few (NPY) nerves were observed. As to the nitrergic innervation, nNOS-containing nerves were very few close to secretory cells and even absent around vessels. Conclusion: The various innervation patterns may suggest potential transmission mechanisms involved in secretory and vascular responses of the major sublingual gland

Fractal diffusion coefficient from dynamical zeta functions

Dynamical zeta functions provide a powerful method to analyze low dimensional dynamical systems when the underlying symbolic dynamics is under control. On the other hand even simple one dimensional maps can show an intricate structure of the grammar rules that may lead to a non smooth dependence of global observable on parameters changes. A paradigmatic example is the fractal diffusion coefficient arising in a simple piecewise linear one dimensional map of the real line. Using the Baladi-Ruelle generalization of the Milnor-Thurnston kneading determinant we provide the exact dynamical zeta function for such a map and compute the diffusion coefficient from its smallest zero.Comment: 8 pages, 2 figure

CO2-Enriched atmosphere on the microscope stage

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Power Corrections in Charmless B Decays

In this paper, we focus on the role of power corrections in QCD factorization(QCDF) method in charmless two-body nonleptonic $B$ meson decays. We use the ratio of the branching fraction of $B^+ \to \pi^+ K^{\ast 0}$ to that of $B^0 \to \pi^- \rho^+$, for which the theoretical uncertainties are greatly reduced, to show clearly that the power corrections in charmless B decays are probably large. With other similar ratios considered, for example, for the $B^0 \to K^- \rho^+$ decay, it is very likely that, among various sources of power corrections, annihilation topology plays an indispensable role at least for penguin dominated $\rm PV$ channels. We also consider some selective ratios of direct CP asymmetries. Among these, we find that, if power corrections other than the chirally enhanced power corrections and annihilation topology were negligible, QCDF would predict the direct CP asymmetry of $B \to \pi^+ \pi^-$ to be about 3 times larger than that of $B \to \pi^\pm K^\mp$, with opposite sign. Experimentally any significant deviation from this prediction would suggest either new physics or possibly the importance of long-distance rescattering effects.Comment: references and note added, to appear in Phys. Rev.

Genetical stability and osteogenic ability of mesenchimal stem cells on demineralized bone matrices

Journal of Osseointegration Volume 7, Issue 1, 1 March 2015, Pages 2-7 Open Access Genetical stability and osteogenic ability of mesenchimal stem cells on demineralized bone matrices (Article) Pozzuoli, A.a, Gardin, C.b, Aldegheri, R.a, Bressan, E.c, Isola, M.d, Calvo-Guirado, J.L.e, Biz, C.a, Arrigoni, P.a, Feroni, L.b, Zavan, B.b a Department of Surgical,Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy b Department of Biomedical Sciences, University of Padua, Padua, Italy c Department of Neurosciences, University of Padua, Padua, Italy d Department of Animal Medicine, Production and Health (MAPS), Italy e Department of General Dentistry, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain Hide additional affiliations View references (44) Abstract Aim: Tissue engineering is a rapidly expanding field with regard to the use of biomaterials and stem cells in the orthopedic surgery. Many experimental studies have been done to understand the best characteristics of cells, materials and laboratory methods for safe clinical applications. The aim of this study was to compare the ability of 2 different human demineralized bone matrices (DBMs), the one enriched and the other not enriched with hyaluronic acid, to stimulate in vitro the proliferation and the osteogenic differentiation of human adipose-derived stem cells (ADSCs) seeded onto an osteoconductive scaffold. Materials and Methods: ADSCs were isolated, by enzymatic digestion, from abdominal adipose tissue of 5 patients undergoing cosmetic lipoaspiration surgery. ADSCs were then seeded onto a 3D scaffold in the presence of the two different osteoinductive matrices of human demineralized bone and evaluated for proliferation and osteogenic differentiation. The safety of the methods was verified using array-Comparative Genomic Hybridization (array-CGH). Results: ADSCs were able to differentiate in osteogenic sense. Both DBMs showed the ability to induce osteogenic differentiation of the cells. Conclusion: array-CGH showed no changes at genome level, thus confirming the safety of materials and method

Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: results of a randomized study

The aim of this trial was to study the value of adding post-operative radiotherapy to lumpectomy in a subgroup of breast cancer patients with favourable patient-, tumour-, and treatment-related prognostic features. 152 women aged over 40 with unifocal breast cancer seen in preoperative mammography were randomly assigned to lumpectomy alone (no-XRT group) or to lumpectomy followed by radiotherapy to the ipsilateral breast (50 Gy given within 5 weeks, XRT group). All cancers were required to be invasive node-negative, smaller than 2 cm in diameter and well or moderately differentiated, to contain no extensive intraductal component, to be progesterone receptor-positive, DNA diploid, have S-phase fraction ≤7 and be excised with at least 1 cm margin. During a mean follow-up time of 6.7 years, 13 (18.1%) cancers recurred locally in the no-XRT and 6 (7.5%) in the XRT group (P = 0.03). There was no difference between the groups in the ultimate breast preservation rate (95.0% vs. 94.4% in XRT and no-XRT, respectively, P = 0.88), distant metastasis-free survival (P = 0.36), or 5-year cancer-specific survival (97.1% in XRT and 98.6 in no-XRT). Radiation therapy given after lumpectomy reduces the frequency of ipsilateral breast recurrences even in women with small breast cancer with several favourable clinical and biological features. However, the breast preservation rate may not increase due to more frequent use of salvage mastectomies in patients treated with postoperative radiotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.co

Influence of the thermophysical properties of pavement materials on the evolution of temperature depth profiles in different climatic regions

The paper summarizes the relative influence of different pavement thermo-physical properties on the thermal response of pavement cross-sections, and how their relative behaviour changes in different climatic regions. A simplified one-dimensional heat flow modelling tool was developed to achieve this using a finite difference solution method for studying the dynamic temperature profile within pavement constructions. This approach allows for a wide variety and daily varying climatic conditions to be applied, where limited or historic thermo-physical material properties are available, and permits the thermal behaviour of the pavement layers to be accurately modelled and modified. The model was used with available thermal pavement materials properties and with properties determined specifically for the study reported here. The pavement materials included in the study comprised both conventional bituminous and cementicious mixes as well as unconventional mixtures that allowed a wide range of densities, thermal conductivities, specific heat capacities and thermal diffusivities to be investigated. Initially, the model was validated against in-situ pavement data collected in the USA in five widely differing climatic regions. It was found to give results at least as good as others available from more computationally expensive approaches such as 2D and 3D FE commercial packages. Then the model was used to compute the response for the same locations had the thermal properties been changed by using some of the unconventional pavement materials been used. This revealed that reduction of temperature range by several degrees was easily possible (with implications for reduction of rutting, fatigue and the Urban Heat Island effect) and that depth of penetration of peak temperatures was also achievable (with implications for winter freeze-thaw). However, the results showed that there was little opportunity to displace the peak temperatures in time

Haemodynamic changes during propofol induction in dogs: New findings and approach of monitoring

Abstract Background Propofol is one of the most widely used injectable anaesthetic agents in veterinary practice. Cardiovascular effects related to propofol use in dogs remain less well defined. The main objective of this study was to evaluate the haemodynamic changes during induction of general anaesthesia with propofol in healthy dogs, by a beat-to-beat continuous monitoring. All dogs were premedicated with intramuscular acepromazine (0.015 mg/kg) and methadone (0.15 mg/kg). Transthoracic echocardiography was used to measure the velocity time integral (VTI) of the left ventricular outflow tract. A syringe driver, programmed to deliver propofol 5 mg/kg over 30 s followed by a continuous infusion of 25 mg/kg/h, was used to induce and maintain anaesthesia. From the initiation of propofol administration, heart rate (HR) and mean invasive arterial blood pressure (MAP) were recorded every 5 s for 300 s, while aortic blood flow was continuously recorded and stored for 300 S. maximum cardiovascular depression was defined the lowest MAP (MAP_Tpeak) recorded during the monitored interval. VTI and VTI*HR were calculated at 0, 30, 90, 120, 150 and 300 s post administration of propofol, and at MAP_Tpeak. Haemodynamic effects of propofol in relation to plasma and biophase concentrations were also evaluated by pharmacokinetics simulation. Results The median (range) HR was significantly higher (p = 0.006) at the moment of maximum hemodynamic depression (Tpeak) [105(70–148) bpm] compared with pre-induction values (T0) [65(50–120) bpm]. The median (range) MAP was significantly lower (p < 0.001) at Tpeak [61(51–69) mmHg] compared with T0 [88(72–97) mmHg]. The median (range) VTI and VTI*HR were similar at the two time points [11.9(8.1–17.3) vs 13,3(9,4-16,5) cm, and 1172(806–1554) vs 1002(630–1159) cm*bpm, respectively]. Conclusions Induction of anaesthesia with propofol causes a drop of arterial pressure in healthy dogs, however cardiac output is well maintained by compensatory chronotropic response. The magnitude of MAP_Tpeak may be strictly related with propofol plasma concentration