Tissue Vessels Research Articles

Balloon catheters with integrated stretchable electronics for electrical stimulation, ablation and blood flow monitoring

Balloon catheter-based techniques that apply mechanical force to blood vessel walls have dramatically advanced the standard of care for patients with vascular disease. But balloons are limited in their therapeutic potential because they rely on mechanics alone and lack electronically active materials. Recent advances in balloon catheters with integrated electrodes have offered additional treatment capabilities through the application of both mechanical contact force and radio frequency electromotive force. However, these smart balloons remain limited in their mechanics and their ability to provide diagnostic information about local vessel hemodynamics and tissue health near treatment zones. Here, we demonstrate a novel instrumented balloon catheter system that contains stretchable electrodes and thermal-based blood flow sensors, providing hemodynamic information, electrical stimulation, and ablation therapy on a single device. This system accommodates high inflation pressure (∼2 atm) and twisting and bending over a broad range of vascular diameters and geometries. Finite element and analytical modeling capture the anisotropic mechanical and thermal properties of the device during cycles of inflation and deflation in a simulated biological environment. Bench-top ablation and in vivo blood flow measurements highlight the utility of this technology for clinical application.

Investigations on the structure and properties of palm leaf sheath fiber

As a natural cellulosic fiber, palm leaf sheath fiber (palm fiber) is widely-distributed and abundant cellulose and engineering fiber resource. To obtain essential information about palm fiber, its morphology, composition, chemical and crystal structure, tensile characteristic and adsorption property were investigated. Test results of palm fiber were compared with those of other natural cellulosic fibers. Palm fiber presents aligned Si-dots on the surface and abundant fiber cells with spiral vessel tissues at the cross section. The chemical composition reveals that palm fiber contains abundant lignin but smaller amount of cellulose (the content of 28.16 %). In addition, investigation illustrates that cellulose in palm fiber is Iβ-dominant type, which is also confirmed by FTIR analysis. X-ray diffraction study shows that the crystallinity (30.52 %), crystallinity index (36.5 %) and crystal size (2.5 nm) are all apparently lower than those of ramie, flax and bamboo fibers. Given the low crystallinity and cellulose content of palm fiber, its tensile strength and Young’s modulus are also lower than those of other fibers. Moreover, palm fiber exhibits excellent breaking elongation, high moisture regain, distinct yield characteristic, and variability in strength. The modified Weibull model was used to study the tensile behavior of palm fiber. This model accurately predicted fiber strength. The absorption volume in isotherm of carbonized palm fiber increases with rising pressure, thus indicating good porous structure of the fiber.

7-Ketocholesterol induces the reduction of KCNMB1 in atherosclerotic blood vessels

Hypertension is a high-risk symptom in atherosclerotic patients, and vascular rigidity is one of the main factors leading to hypertension. β1-Subunit of BKCa channel (KCNMB1; MaxiKβ1) has been reported as a modulator of vascular flexibility. To determine the relationship between atherosclerosis and KCNMB1, we studied some atherogenic factors affecting vascular tone. Blood of atherosclerotic patients shows increased concentration of 7-ketocholesterol (7K), which has been studied as a harmful lipid to blood vessels. Our data showed that KCNMB1 was significantly down-regulated in the presence of 7K, in a dose-/time-dependent manner in vascular smooth muscle cells (VSMCs). And, the reduction of KCNMB1 was confirmed in cell images of 7K-stimulated VSMCs and in vessel tissue images of ApoE knock-out mice. To determine whether aryl hydrocarbon receptor (AhR) was involved in the reduction of KCNMB1 by 7K-stimulation, protein level of AhR was analyzed by Western blot. Our data showed that the reduction of KCNMB1 was modulated through the AhR pathway. In conclusion, results of our study suggest that 7K induces the reduction of KCNMB1 through the AhR pathway.

Software and hardware systems for abdominal aortic aneurysm mechanical properties investigation

The main goal of this paper is to describe two different systems that were developed for the purpose of abdominal aortic aneurysm mechanical properties investigation and to present the results of the measurements. The first system is based on the “Bubble Inflated” method and it increases the pressure of physiological saline which affects blood vessel tissue and causes mechanical deformation. The system provides recording the data about the current value of the pressure in the physiological saline by using the appropriate pressure sensor. The second system makes stretches of the vessel tissue in uni-axial direction and save the data about the force and the elongation. Both of these systems use cameras for assessment of the deformation. Obtained results from both systems are used for numerical simulation of computer model for abdominal aortic aneurysm. It gives a new avenue for application of software and hardware systems for determination of vascular tissue properties in the clinical practice.

Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury.

The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

Intraoperative localization and protection of important structures of the neck in thyroid surgery

Nodular thyroid disease affects thousands of people in Poland. Tumors of the thyroid account for about 1% overall human cancers. Thyroidectomy is the most common surgical operation in endocrine tumors. Operative therapy for benign thyroid nodules is recommended for: progressive increase in nodule size, substernal extension, compressive symptoms of the neck, the development of thyrotoxicosis and patient therapeutic prevalence. In Poland thyroidectomy is the fifth surgical procedure and comprises about 25000 operations yearly. Reduction of surgical injury with simultaneous retention of current safety and radical nature of surgical intervention forces the work into a relatively small operating field. Electric devices enabling the achievement of full and lasting haemostasis during thyroidectomy supplant traditional surgical method (ligature, haemostatic sutures) with no impact on the incidence of perioperative complications, while at the same time allowing to shorten the duration of the procedure. The haemostatic effect is associated with generation of heat, which apart from the intended result may bring about thermal tissue injury. During the surgical procedure it is important to determine the thermal spread around the active tip of electric devices in the operating field during thyroidectomy, and the safe temperature range during the operation to protect important structures of the neck. The mean safe distance of the active tip of an electric device from important anatomic structures is 5mm minimally and depends on the device type, time of operation and its power settings. All the modern techniques of vessel sealing are associated with generation of heat and its spherical spread, which causes thermal injury to the surrounding tissues. Their mode of operation through, among others, structural changes in collagen and elastin, leads to durable connection of sealed vessel walls and tissue structures. These systems enable a safe sealing of vessels of up to 7 mm in diameter. In conclusions: In the cases analyzed by the author concerning the thyroidectomy techniques, it is recommended to replace electric devices with ligatures or clips or human fibrinogen in place near the laryngeal nerves, parathyroid glands and the trachea. The decision of the change of the method of haemostasis maintenance in the vicinity of crucial structures has been left to the surgeon.

Small Diameter Coronary Arteria Designed In Vitro

Although the necessity for a useful blood vessel replacement is evident, the lower blood flow velocities of smalldiameter arteries just like the arterial blood vessel have semiconductor diode to the failure of artificial materials that are triple-crown for large-diameter grafts. Though autologous vessels stay the quality for little diameter grafts, several patients don't have a vessel appropriate to be used owing to vascular unwellness, amputation, or previous harvest. As a result, tissue engineering has emerged as a promising approach to deal with the shortcomings of current therapies. Investigators have explored the utilization of blood vessel tissue cells or differentiated stem cells combined with numerous kinds of natural and artificial scaffolds to form cannular constructs and subject them to chemical and/or mechanical stimulation in an endeavor to develop a useful small-diameter blood vessel replacement graft with variable degrees of success. Here, we tend to review the progress all told these major sides of the sector.

Engineering aligned electrospun PLLA microfibers with nano-porous surface nanotopography for modulating the responses of vascular smooth muscle cells.

In tissue engineering research, aligned electrospun ultrafine fibers have been shown to regulate cellular alignment and relevant functional expression, but the imposed effect of individual fiber surface nanotopography on cell behaviour has not been examined closely. This work investigates the impact of superimposing a nano-pore feature atop individual fiber surfaces on the responsive behaviour of human vascular smooth muscle cells (vSMCs) for blood vessel tissue engineering. Well-aligned ultrafine poly(l-lactic acid) (PLLA) microfibers with an average fiber diameter of ca. 1.6 μm were fabricated by using a novel stable jet electrospinning (SJES) method. Ellipse-shaped nano-pores with varied aspect ratios (defined as long-to-short axis ratio) of 2.7-3.9, corresponding to a surface nano-roughness in the range of 54.8-110.0 nm, were in situ generated onto individual fiber surfaces by varying ambient humidity from 45% to 75% during the SJES process. The presence of elliptical nano-pores on fiber surfaces affected the characteristic anisotropic wettability of the aligned PLLA fibers and contributed to greater protein adsorption (up to 17.59 μg mg-1). A 7 day in vitro assessment of human umbilical arterial SMCs cultured on these aligned nano-porous fiber substrates indicated that cellular responses were in close correlation with the elliptical nano-pore feature. A pronounced fiber surface nanotopography was superior in soliciting favorable cellular responses, leading to enhanced cell attachment, proliferation, alignment, expression of the vascular matrix proteins and maintenance of a contractile phenotype. This study thus suggests that introduction of an elliptical nano-pore feature to the aligned microfiber surfaces could provide additional dimensionality of topographical cues to modulate the vSMC responses when using the aligned electrospun ultrafine fibers for engineering vascular constructs.

Identification and functional characterization of FGLamide-related allatostatin receptor in Rhodnius prolixus

FGLamide-related ASTs (FGLa/ASTs) are a family of brain/gut peptides with numerous physiological roles, including inhibition of juvenile hormone (JH) biosynthesis by the corpora allata and inhibition of visceral muscle contraction. FGLa/ASTs mediate their effects by binding to a rhodopsin-like G-protein coupled receptor that is evolutionarily related to the vertebrate galanin receptor. Here we determine the cDNA sequence encoding FGLa/AST receptor (FGLa/AST-R) from the Chagas disease vector, Rhodnius prolixus (Rhopr-FGLa/AST-R), determine its spatial expression pattern using quantitative PCR and functionally characterize the receptor using a heterologous assay. Our expression analysis indicates that Rhopr-FGLa/AST-R is highly expressed in the central nervous system. The receptor is also expressed in various peripheral tissues including the dorsal vessel, midgut, hindgut and reproductive tissues of both males and females, suggesting a role in processes associated with feeding and reproduction. The possible involvement of Rhopr-FGLa/ASTs in the inhibition of JH biosynthesis is also implicated due to presence of the receptor transcript in the R. prolixus corpora cardiaca/corpora allata complex. The functional assay showed that various Rhopr-FGLa/ASTs activate the receptor, with EC50 values for the response in the nanomolar range. Moreover, Rhopr-FGLa/AST-R can couple with Gq alpha subunits and cause an increase in intracellular calcium concentration. Lastly, we tested various FGLa/AST analogs in our heterologous assay. These compounds also activated the receptor and thus have the potential to serve as insect growth regulators and aid in pest control.

ASSA14-12-07 In vitroandin vivobiocompatibility evoluation of New vascular embolization agent:

Obejective In this paper, the thrombins were encapsulated in calcium-alginate microspheres using electrostatic droplet technique to produce a new embolic agents: Thrombin-loaded Alginate-Calcium Microspheres (TACM), which were used chiefly to control bleeding in blunt abdominal trauma. However, the use of the embolisation in clinical practice requires a thorough understanding of the biocompatibility of TACM. The present work examined the biocompatibility of TACM from aspect of a series of in-vitro and in-vivo experiments. Methods After TACM were successfully prepared, the size distribution and morphology of TACM were evualuated. the biocompatibility of TACM in vitro were examined by assessing the cell viability of vascular endothelial cells (VECs), whole blood hemolysis, and inflammatory potential of TACM. In vivo , a dog liver superselective embolization was performed with TACM, after 48 h, 4 w and 12 w, acute, mid and long term biocompatibility were studied by evualuating clinical, biochemical and tissue response. Results co-culture with VECs revealed non-cytotoxic of TACM compared to monolayer control (P ≥ 0.05), hemolysis was negligible and cytokines release from PBMC shows significant decrease relative to LPS group (p ≤ 0.05). Furthermore, no measurable clinical and biochemical toxic effects were observed in any of animals. The histological study of liver blood vessels tissue shows low inflammation, and the Banff 97 score was only 0.08 ± 0.18 at 48 h and then decrease to 0.04 ± 0.12 at 12 w. correspondingly, the giant cell score were 0.00 ± 0.00, 0.07 ± 0.25, 0.12 ± 0.18 at 48 h, 4 w and 12 w respectively. Conclusions Both in vitro and in vivo data shows good biocompatibility of TACM, and it can be applied safely in futher clinical reaserch.

Abstract 16722: Changes in Carotid Wall Morphology and Plaque Composition in Patients With Established Vascular Disease and Treated With Intensive Lipid Therapy in the AIM-HIGH Study

Objective: Changes in carotid wall morphology (MORPH) and plaque composition (COMP) over 2 years (yrs) of intensive lipid therapy by plaque types were investigated in AIM-HIGH. Methods: Qualified baseline and 2-yr follow-up scans were obtained in 156 AIM-HIGH subjects. MR images were analyzed by independent Core Lab reviewers using published criteria for quantifications of MORPH and COMP. MORPH included volumes of total vessel (TVV), lumen (LV), wall (WV=TVV-LV) and fibrous tissue (FTV) in mm3 and %WV was calculated using the formula: (WV/TVV) X 100% in all available slices. COMP focused on percentages of lipid-rich necrotic core (%LRNC), FT (%FT) and calcium (%CA) calculated using the formula: (LRNC, FT or CA V/WV) x 100% using the slices containing LRNC. Of 156, 89 were in statin+placebo for extended-release niacin (ERN) and 67 in statin+ERN groups. Changes in MORPH and COMP were compared between the 2 treatment groups and between plaque types: w/o LRNC (n=76), w/ LRNC but w/o intraplaque hemorrhage (IPH) (n=62), w/ LRNC & IPH (n=18). Results: In the 76 subjects w/o LRNC, there were significant increases in TVV (24±52 mm3/yr, p<0.001), LV (14±40 mm3/yr, p<0.01), WV (10±26 mm3/yr, p=0.002) and FTV (10±26 mm3/yr, p=0.002) while %WV was relatively stable (0.04±1.0%, p=0.48) over 2yrs. In the 62 w/ LRNC but w/o IPH, the slices containing LRNC showed a significant decrease in %LRNC (1.05±2.6%/yr, p=0.001) and significant increases in %FT (0.85±2.7%/yr, p=0.01) and %CA (0.20±0.63%/yr, p=0.002), although corresponding MORPH did not change significantly. By contrast, LRNC plaques w/ IPH tended to increase in %LRNC (1.4±3.2/yr) and decrease in %FT (1.4±3.0%/yr). These rates were significantly different from those of the LRNC plaques w/o IPH (p=0.008 and 0.012, respectively). These MORPH and COMP measures did not differ significantly between statin+placebo and statin+ERN groups. Conclusions: Intensive lipid therapy with statin or statin plus ERN significantly associated with positive MORPH remodeling in plaques w/o LRNC. Plaques w/ LRNC experienced COMP improvement without significant MORPH changes. However, the COMP improvement was not seen in plaques w/ IPH. These results indicate that plaques in different disease stages respond to lipid therapy differently.

Characterizing the contrast of white matter and grey matter in high-resolution phase difference enhanced imaging of human brain at 3.0 T.

The purpose of this study was to address the feasibility of characterizing the contrast both between and within grey matter and white matter using the phase difference enhanced (PADRE) technique. PADRE imaging was performed in 33 healthy volunteers. Vessel enhancement (VE), tissue enhancement (TE), and PADRE images were reconstructed from source images and were evaluated with regard to differentiation of grey-to-white matter interface, the stria of Gennari, and the two layers, internal sagittal stratum (ISS) and external sagittal stratum (ESS), of optic radiation. White matter regions showed decreased signal intensity compared to grey matter regions. Discrimination was sharper between white matter and cortical grey matter in TE images than in PADRE images, but was poorly displayed in VE images. The stria of Gennari was observed on all three image sets. Low-signal-intensity bands displayed in VE images representing the optic radiation were delineated as two layers of different signal intensities in TE and PADRE images. Statistically significant differences in phase shifts were found between frontal grey and white matter, as well as between ISS and ESS (p < 0.01). The PADRE technique is capable of identifying grey-to-white matter interface, the stria of Gennari, and ISS and ESS, with improved contrast in PADRE and TE images compared to VE images. • Phase difference enhanced (PADRE) imaging can yield diverse contrasts between tissues • The PADRE technique utilizes the inherent variety of magnetic susceptibilities • PADRE MR imaging provides better visualization of certain cerebral anatomy in vivo • PADRE imaging is able to delineate the stria of Gennari in the primary visual cortex • PADRE imaging is able to identify the two optic radiation layers.

Общие патогенетические механизмы атеросклероза и остеопороза: эластичность артериальной стенки и минеральная плотность кости в зависимости от некоторых параметров репликативного клеточного старения

The review concerns on the common pathogenetic mechanisms of the atherosclerosis and osteoporosis development, and vessel wall elasticity with the decrease of bone mass and changes in bone metabolism. In addition, the results of clinical trials are studied on the exploration of the interconnection between vessel calcification, vessel rigidity values and endurance of the bone tissue. Presence of the common pathogenetic mechanisms in age-dependent diseases with the same molecular markers and serious genetic determination of mineral bone density and vessel calcification creates preterm for the search for common cell markers of early vessel and mone tissue ageing. As the clinical evaluation of the ageing and age-dependent diseases is more linked with the specific problems of their asymptomatic course, during modern period investigators are at most concerned with various informative biomarkers of ageing and the risk of development and prognosis of the diseases’ outcomes. As the role of such common cell markers, which are easy to study in blood leucocytes, the telomeres (length) pretend and telomerase activity.

Noncontact Vibration Measurement Based Thoracic Spine Condition Monitoring During Pedicle Drilling

In order to prevent possible damage to the spinal cord, blood vessel or other soft tissues, reliable monitoring methods are required to provide valuable information on the condition of the bone being cut. A method is proposed for monitoring thoracic spine conditions via the use of bone vibration signal during pedicle drilling, which is directly recorded by a noncontact laser displacement sensor. The main reason to cause axial vibration of drill bit is analyzed, and the main frequencies composing the vibration signal are integer multiples of spindle frequency. Then, we analyze the vibration feature of cancellous and cortical bone under this harmonic excitation. Wavelet packet transform is performed to extract the crucial characteristic from the measured data to correlate drilling condition. The safe and dangerous drilling operations are discriminated by the comparison of harmonic energy ratio over some characteristic scales. The proposed method is experimentally verified through the drilling operation in porcine spines, and the results are in accordance with the theoretical analysis and then the safety of the drilling operation is improved.

Abstract 2276: Induction of apoptosis and inhibition of angiogenesis by novel fusion protein - AD-O54.9 as a new preclinical strategy in cancer treatment

Abstract Background For almost two decades tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) has been under extensive development as a potential therapeutic agent. TRAIL/Apo2L is a member of the TNF superfamily with unique ability to induce apoptosis in cancer cells while remaining neutral to normal cells. Tumor growth is tightly related to new blood vessel formation and tissue remodeling. Platelet derived growth factor (PDGF) is important in vascular physiological and pathological development. Inhibition of PDGF pathway blocks angiogenesis what results in reduction of tumor growth. We proposed a novel fusion protein (AD-O54.9) with dualistic proapoptotic and antiangiogenic activity. Our molecule consists of the soluble recombinant TRAIL/Apo2L variant linked with an effector peptide sequence and an activation motif recognized by tumor-specific proteases (MMPs, uPa) between. The effector peptide is composed of 19-amino acid fragment derived from human PDGF, which binds the PDGF receptors competitively to the natural ligand while being itself devoid of activity. As a consequence, angiogenic activity of PDGF is blocked, stimulation of new blood vessels formation does not occur and finally tumor growth is inhibited. Materials and methods AD-O54.9 protein was expressed in E. coli, using pET expression system, and purified by IEC chromatography. Cytotoxic activity of AD-O54.9 was examined using a propidium iodide assay and its antiangiogenic activity was evaluated by HUVEC tube formation and ring aortic assays. Safety was tested on human primary hepatocytes. The proapoptotic and antiproliferative activity was tested using molecular biology and flow cytometry methods. In vivo potential was examined on mice xenograft models of human colorectal adenocarcinoma (Colo205), human lung carcinoma (NCI-H460-luc2), human pancreatic carcinoma (MIA PaCa-2) and human oesophageal adenocarcinoma (OE19) cell lines where molecules showed anticancer activity. Results The molecule showed in vitro specific cytotoxic effect on various primary cancer cell lines at IC50 below 0.01 ng/ml. We demonstrated that AD-O54.9 is a very potent apoptosis inducer and inhibitor of angiogenesis. This fusion protein showed superior efficacy displaying significant tumor volume regression compared with TRAIL/Apo2L and standard chemotherapeutic agents. Conclusions The obtained results confirm that we developed a very promising fusion molecule with a high potential of anticancer activity that could be considered as a novel therapeutic agent. Citation Format: Piotr Rózga, Jerzy Pieczykolan, Bartłomiej Zerek, Anna Pieczykolan, Marlena Gałązka, Katarzyna Bukato, Michał Szymanik, Albert Jaworski, Sebastian Pawlak, Małgorzata Teska-Kamińska, Anna Grochot-Przęczek. Induction of apoptosis and inhibition of angiogenesis by novel fusion protein - AD-O54.9 as a new preclinical strategy in cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2014-2276

Electrospun tecophilic/gelatin nanofibers with potential for small diameter blood vessel tissue engineering.

Tissue engineering techniques particularly using electrospun scaffolds have been intensively used in recent years for the development of small diameter vascular grafts. However, the development of a completely successful scaffold that fulfills multiple requirements to guarantee complete vascular regeneration remains challenging. In this study, a hydrophilic and compliant polyurethane namely Tecophilic (TP) blended with gelatin (gel) at a weight ratio of 70:30 (TP(70)/gel(30)) was electrospun to fabricate a tubular composite scaffold with biomechanical properties closely simulating those of native blood vessels. Hydrophilic properties of the composite scaffold induced non-thrombogenicity while the incorporation of gelatin molecules within the scaffold greatly improved the capacity of the scaffold to serve as an adhesive substrate for vascular smooth muscle cells (SMCs), in comparison to pure TP. Preservation of the contractile phenotype of SMCs seeded on electrospun TP(70)/gel(30) was yet another promising feature of this scaffold. The nanostructured TP(70)/gel(30) demonstrated potential feasibility toward functioning as a vascular graft.

The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels.

Intermediate-conductance Ca2+-activated K+ (IK) channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I) as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG) in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.

Leiomyosarcoma in a Posthysterectomy Patient

ABSTRACT Leiomyosarcoma is an aggressive soft tissue sarcoma derived from smooth muscle cells. Uterus is the commonest location for a leiomyosarcoma. They may either arise de novo from uterine musculature or the connective tissue of uterine blood vessels, or in a pre-existing benign leiomyoma and are associated with poor outcome. A 45 year patient presented with mass per abdomen. She had under gone laparoscopic hysterectomy three years back for menorrhagia. A provisional diagnosis of ovarian neoplasm was made based on the ultrasonography and CT scan report, but tumour markers were negative. Staging laparotomy was done, mass removed in toto, infracolic omentectomy, appendectomy and bilateral ureteric dissection was done. Post operatively, patient recovered well. Histopathological analysis was suggestive of leiomyosarcoma FNCLCC grade 3. Patient was advised radiation and is on regular follow up with the oncosurgeon. How to cite this article Agarwal M, Hegde S, Sawapure N. Leiomyosarcoma in a Posthysterectomy Patient. Int J Gynecol Endsc 2017;1(1):50-52.

Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues.

Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include “traditional” IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems.

Activated platelet supernatant can augment the angiogenic potential of human peripheral blood stem cells mobilized from bone marrow by G-CSF

Platelets not only play a role in hemostasis, but they also promote angiogenesis and tissue recovery by releasing various cytokines and making an angiogenic milieu. Here, we examined autologous ‘activated platelet supernatant (APS)’ as a priming agent for stem cells; thereby enhance their pro-angiogenic potential and efficacy of stem cell-based therapy for ischemic diseases. The mobilized peripheral blood stem cells (mobPBSCs) were isolated from healthy volunteers after subcutaneous injection of granulocyte-colony stimulating factor. APS was collected separately from the platelet rich plasma after activation by thrombin. mobPBSCs were primed for 6h before analysis. Compared to naive platelet supernatants, APS had a higher level of various cytokines, such as IL8, IL17, PDGF and VEGF. APS-priming for 6h induced mobPBSCs to express key angiogenic factors, surface markers (i.e. CD34, CD31, and CXCR4) and integrins (integrins α5, β1 and β2). Also mobPBSCs were polarized toward CD14(++)/CD16(+) pro-angiogenic monocytes. The priming effect was reproduced by an in vitro reconstruction of APS. Through this phenotype, APS-priming increased cell–cell adhesion and cell–extracellular matrix adhesion. The culture supernatant of APS-primed mobPBSCs contained high levels of IL8, IL10, IL17 and TNFα, and augmented proliferation and capillary network formation of human umbilical vein endothelial cells. In vivo transplantation of APS-primed mobPBSCs into athymic mice ischemic hindlimbs and Matrigel plugs elicited vessel differentiation and tissue repair. In safety analysis, platelet activity increased after mixing with mobPBSCs regardless of priming, which was normalized by aspirin treatment. Collectively, our data identify that APS-priming can enhance the angiogenic potential of mobPBSCs, which can be used as an adjunctive strategy to improve the efficacy of cell therapy for ischemic diseases.