Tissue Reactivity Research Articles

759 Effects of High Comorbidity in Patients With Intraductal Papillary Mucinous Neoplasms: A Single Center Analysis of 725 Patients

Pancreas features extensive ductal and neurovascular networks in association with acini and islets to perform exocrine and endocrine functions. However, due to the dispersed nature of the network architecture, the standard microtome-based histology cannot provide a globe view of the pancreatic tissue networks in health and disease. To overcome this challenge, we prepared transparent pancreatic specimens by optical clearing (use of immersion solution of high refractive index to promote tissue photon penetration; Tang et al., Diabetes, Obesity and Metabolism, 2014, doi: 10.1111/dom.12342) and performed 3-D microscopy with tile scanning to reveal the spatial features of the pancreatic ductal and neurovascular networks with high definition. Mouse pancreatic intraepithelial neoplasia (PanIN) was induced by activation of oncogenic Kras in acinar cells and/or caerulein injections (chronic pancreatitis). Taking advantage of the transparent tissue, we simultaneously revealed the 3-D PanIN microstructure and the associated neurovascular environment in an integrated fashion. Perilesional neural tissue outgrowth (sympathetic neurite outgrowth and gliosis) and an increase in pericyte marker density were identified via in-depth image projection, indicating the reactivity of the pancreatic neurovascular tissues in response to lesion formation. Overall, the global characterization of duct lesions highlights the advantage of using 3-D microscopy to explore the unknown details of the pancreatic microenvironment in PanIN development.

758 3-D Imaging of Mouse Pancreatic Duct Lesion and Neurovascular Remodeling

Pancreas features extensive ductal and neurovascular networks in association with acini and islets to perform exocrine and endocrine functions. However, due to the dispersed nature of the network architecture, the standard microtome-based histology cannot provide a globe view of the pancreatic tissue networks in health and disease. To overcome this challenge, we prepared transparent pancreatic specimens by optical clearing (use of immersion solution of high refractive index to promote tissue photon penetration; Tang et al., Diabetes, Obesity and Metabolism, 2014, doi: 10.1111/dom.12342) and performed 3-D microscopy with tile scanning to reveal the spatial features of the pancreatic ductal and neurovascular networks with high definition. Mouse pancreatic intraepithelial neoplasia (PanIN) was induced by activation of oncogenic Kras in acinar cells and/or caerulein injections (chronic pancreatitis). Taking advantage of the transparent tissue, we simultaneously revealed the 3-D PanIN microstructure and the associated neurovascular environment in an integrated fashion. Perilesional neural tissue outgrowth (sympathetic neurite outgrowth and gliosis) and an increase in pericyte marker density were identified via in-depth image projection, indicating the reactivity of the pancreatic neurovascular tissues in response to lesion formation. Overall, the global characterization of duct lesions highlights the advantage of using 3-D microscopy to explore the unknown details of the pancreatic microenvironment in PanIN development.

The Procedural Pause

The Procedural Pause

Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits.

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with the structure and proteins of the pellicle layer, as well as microbes in the biofilm, remains unclear. The tooth enamel is a dense crystalline structure that is likely to act as a barrier to ENM penetration, but underlying dentinal tubules are not. Consequently, ENMs may be used to strengthen dentine or regenerate pulp tissue. ENMs have dental applications as antibacterials for infection control, as nanofillers to improve the mechanical and bioactive properties of restoration materials, and as novel coatings on dental implants. Dentifrices and some related personal care products are already available for oral health applications. Overall, the clinical benefits generally outweigh the hazards of using ENMs in the oral cavity, and the latter should not prevent the responsible innovation of nanotechnology in dentistry. However, the clinical safety regulations for dental materials have not been specifically updated for ENMs, and some guidance on occupational health for practitioners is also needed. Knowledge gaps for future research include the formation of protein corona in the oral cavity, ENM diffusion through clinically relevant biofilms, and mechanistic investigations on how ENMs strengthen the tooth structure.

Lectins: getting familiar with translators of the sugar code.

The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical properties endow carbohydrates to form oligomers with unsurpassed structural variability. Owing to their capacity to engage in hydrogen (and coordination) bonding and C-H/π-interactions these “code words” can be “read” (in Latin, legere) by specific receptors. A distinct class of carbohydrate-binding proteins are the lectins. More than a dozen protein folds have developed carbohydrate-binding capacity in vertebrates. Taking galectins as an example, distinct expression patterns are traced. The availability of labeled endogenous lectins facilitates monitoring of tissue reactivity, extending the scope of lectin histochemistry beyond that which traditionally involved plant lectins. Presentation of glycan and its cognate lectin can be orchestrated, making a glycan-based effector pathway in growth control of tumor and activated T cells possible. In order to unravel the structural basis of lectin specificity for particular glycoconjugates mimetics of branched glycans and programmable models of cell surfaces are being developed by strategic combination of lectin research with synthetic and supramolecular chemistry.

Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal cancer and normal tissues.

Special AT-rich sequence-binding protein 1 (SATB1) is a ‘genome organizer,’ and it has been proposed as a factor that affects the development and progression of various human neoplasms, including colorectal cancer (CRC). This study aimed to compare SATB1 expression in a group of CRC patients and healthy subjects at the mRNA and protein levels. We collected paired tumor tissue and unchanged mucosa of the large intestine from 102 CRC patients as well as 53 biopsies of normal colon mucosa obtained from healthy patients during screening colonoscopy. Tissue samples were quantified for SATB1 mRNA by quantitative PCR, while SATB1 protein expression was determined by Western blotting and immunohistochemistry. SATB1 mRNA level in tumor tissues was over twofolds lower than in samples of corresponding unchanged tissues and fourfolds lower than in biopsies of healthy colon mucosa. Western blotting analysis revealed that SATB1 protein content in tumor and unchanged tissues of CRC patients was over sixfold and fivefolds higher than in biopsies of healthy colon mucosa, respectively. Immunohistochemical staining demonstrated higher nuclear and cytoplasmic SATB1 reactivity in the tumor tissue compared to unchanged mucosa of CRC patients. Despite these differences, SATB1 mRNA, protein, and immunoreactivity levels did not correlate with patients’ clinicopathological data and their overall survival, but the latter analysis was limited by a relatively short period of follow-up. In conclusion, we suggest that some as yet unidentified posttranscriptional mechanisms that regulate SATB1 expression may be altered in the CRC tissue.

Donor-specific antibodies, C4d and their relationship with the prognosis of transplant glomerulopathy.

Transplant glomerulopathy (TG) is a diagnostic criterion for chronic active antibody-mediated rejection (CAABMR), with C4d, donor-specific antibodies (DSA) and other lesions of chronic tissue injury. However, TG often presents without C4d or DSA. Until recently, such cases were termed suspicious for CAABMR, and their prognosis remains unclear. To better understand the contribution of TG, C4d, and DSA on outcomes, we retrospectively studied 61 patients with late TG for the composite endpoint of death-censored graft failure or doubling of serum creatinine. Cases were matched to controls based on age, year and number of transplant, type of donor, and the availability of an indication biopsy during the same time after transplantation. Analyses were performed using proportional hazards models. Compared to matched controls, patients with TG had a more than fivefold increased risk of reaching the endpoint (adjusted hazard ratio (aHR), 5.3; 95% confidence interval (95% CI), 1.5-18.4). The proportion of patients with isolated TG, TG suspicious for CAABMR (C4+/DSA- or C4d-/DSA+) and TG with definite CAABMR (C4d+/DSA+) were 63%, 20%, and 17%, respectively. Suspicious and definite CAABMR showed a similar prognosis, significantly worse than isolated TG (aHR, 4.5; 95% CI, 1.1-18.9 and aHR, 5.9, 95% CI, 1.1-31.3 respectively). Transplant glomerulopathy is associated with poor prognosis, independent of the level of graft dysfunction and other chronic histologic changes. This prognosis is similar whether there is evidence of tissue or peripheral alloantibody reactivity. These findings are relevant to the development of clinically meaningful criteria for CAABMR, for its clinical management, and in the future selection of population for clinical trials.

Immunoreaction of 14F7 Mab Raised against N-Glycolyl GM3 Ganglioside Correlates with High Histological Grade in some Tumors of Neuroectodermal and Epithelial Lineage

The aberrant expression of N-glycolyl GM3 ganglioside (NeuGcGM3) has been reported in a variety of malignant tumors. Nevertheless, the relationship between NeuGcGM3 expression and aggressive biological behavior still remains unclear for the majority of malignancies. In this article the tissue reactivity of the 14F7 monoclonal antibody, a highly specific IgG1 against NeuGcGM3, in breast cancer, urinary bladder tumors and malignant gliomas of adult patients is shown as well as its relation with the histological grade of these malignancies. The expression of NeuGcGM3 was detected in 92/155 (59.3%) of tumors independently of the histopathological classification. However, a preferential expression of NeuGcGM3 was detected in: infiltrating ductal carcinoma (77.1%) vs. infiltrating lobular carcinoma (15.9%) (p=0.024), grade III (94.9%) vs. grade II (77.8%) and grade I (63.8%) transitional cell carcinoma (p=0.042) and high-grade astrocytomas (78.6%) vs. low-grade astrocytic tumors (10.0%) (p=0.026). The results achieved suggest the relationship between the tissue expression of NeuGcGM3 and the more aggressive biological behavior of these malignancies, regardless of the tumor cell lineage. The data obtained also support the continuous use of NeuGcGM3 as a target for immunotherapy in malignancies expressing this molecule as well as that of 14F7 monoclonal antibody for the selection of candidate patients for these specific therapies.

Tissue adhesives for closure of surgical incisions.

Sutures (stitches), staples and adhesive tapes have been used for many years as methods of wound closure, but tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables the closure to be meticulous, but the sutures may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no requirement to remove sutures later. Initially, tissue adhesives were used primarily in emergency room settings, but this review looks at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin incisions. To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical wounds. In March 2014 for this second update we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of publication or study setting. Only randomised controlled trials were eligible for inclusion. We conducted screening of eligible studies, data extraction and risk of bias assessment independently and in duplicate. We expressed results as random-effects models using mean difference for continuous outcomes and risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We investigated heterogeneity, including both clinical and methodological factors. This second update of the review identified 19 additional eligible trials resulting in a total of 33 studies (2793 participants) that met the inclusion criteria. There was low quality evidence that sutures were significantly better than tissue adhesives for reducing the risk of wound breakdown (dehiscence; RR 3.35; 95% CI 1.53 to 7.33; 10 trials, 736 participants that contributed data to the meta-analysis). The number needed to treat for an additional harmful outcome was calculated as 43. For all other outcomes - infection, patient and operator satisfaction and cost - there was no evidence of a difference for either sutures or tissue adhesives. No evidence of differences was found between tissue adhesives and tapes for minimising dehiscence, infection, patients' assessment of cosmetic appearance, patient satisfaction or surgeon satisfaction. However there was evidence in favour of using tape for surgeons' assessment of cosmetic appearance (mean difference (VAS 0 to 100) 9.56 (95% CI 4.74 to 14.37; 2 trials, 139 participants). One trial compared tissue adhesives with a variety of methods of wound closure and found both patients and clinicians were significantly more satisfied with the alternative closure methods than the adhesives. There appeared to be little difference in outcome for different types of tissue adhesives. One study that compared high viscosity with low viscosity adhesives found that high viscosity adhesives were less time-consuming to use than low viscosity tissue adhesives, but the time difference was small. Sutures are significantly better than tissue adhesives for minimising dehiscence. In some cases tissue adhesives may be quicker to apply than sutures. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in the operating theatre, they need to be aware that sutures minimise dehiscence. There is a need for more well designed randomised controlled trials comparing tissue adhesives with alternative methods of closure. These trials should include people whose health may interfere with wound healing and surgical sites of high tension.

Abstract 2801: The use of induced pluripotent stem (iPS) cells for the safety testing of enhanced affinity TCR-transduced T cells

Abstract Engineering T cells with enhanced affinity T cell receptors (TCRs) is a promising therapeutic strategy for treating cancer. Engineered TCRs overcome the limitations of naturally occurring cancer-antigen specific TCRs which are typically of extremely low affinity and fail to efficiently recognize tumor cells. However, the use TCRs with enhanced affinity for adoptive therapy carries with it the risk that they might recognize normal tissue, either as on-target or off-target reactivity. Two fatalities in a clinical trial of an affinity-enhanced MAGE-A3-specific TCR have highlighted the need for more biologically relevant cellular testing systems to minimize cross-reactivity-related toxicity in future adoptive immunotherapy trials. Cellular Dynamics International Inc. supply a range of iCell products that are highly pure induced pluripotent stem (iPS) cell-derived cells that reproduce normal human biology in an in vitro setting. The advantage of iCell cultures over standard cultures of primary cells is that they better represent human organs with respect to their antigen presentation by HLA. In this study, a panel of iCell sub-types, representing major organs of the human body, were used to test the reactivity of T cells transduced with an enhanced affinity TCR for HLA-A2-restricted peptide antigen NY-ESO-1/LAGE-1157-165. IncuCyte FLR technology, which enables direct visualization of caspase-3/7-dependent apoptosis at 37°C in real time, was used to assess the killing of the iCells by NY-ESO TCR-transduced T cells over a 4 day time course. While potent killing by the NY-ESO TCR-transduced T cells was observed against an HLA-A2+, NY-ESO-1+/LAGE-1+ tumor cell line, A375, no reactivity was observed against any of the tested iCells sub-types unless the iCells were pulsed with 1 µM NY-ESO peptide. The screening of TCR-transduced T cells against biologically appropriate cell cultures, such as iCells, further advances preclinical safety testing of new TCRs for use in adoptive immunotherapy. Citation Format: Katherine J. Adams, Andrew B. Gerry, Joanna E. Brewer, Nicholas J. Pumphrey, Alan D. Bennett, Bent K. Jakobsen. The use of induced pluripotent stem (iPS) cells for the safety testing of enhanced affinity TCR-transduced T cells. [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 2801. doi:10.1158/1538-7445.AM2014-2801

Scleral collagen crosslinking (SXL) by riboflavin and blue light inhibits eye growth of young rabbits

AbstractPurpose The application of riboflavin and blue light (for Collagen Crosslinking of scleral tissue; SXL) was proved as a possible therapeutic method to increase scleral stiffness and therefore, to inhibit eye growth in young rabbits.Methods For eye growth examination the sclera of young rabbit eyes were treated with riboflavin and 10 mW/cm² blue light. MR‐Imaging and ultrasonic A scans were used to measure effects of SXL treatment on eye growth. Safety and efficacy parameters were determined using immunohistochemical and histological methods.Results Immunohistochemical and histological examinations showed no neurodegenerative side effects or signs of glial reactivity in retinal tissue beyond a light intensity of 400 mW/cm². Young animals treated with a minimal effective light energy dose of 10 mW/cm² displayed a significant reduction of their eye growth. The eye growth inhibition after SXL treatment maintained for at least 24 weeks.Conclusion The results confirm the idea that scleral collagen crosslinking by riboflavin/blue light is an applicable method to inhibit eye growth and therefore, it might be a treatment for pathologic myopia.

A structural framework for interpretation of four-electrode microimpedance spectra in cardiac tissue.

Renewed interest in the four-electrode method for identification of passive electrical properties in cardiac tissue has been sparked by a recognition that measurements made with sensors in close proximity are frequency dependent. Therefore, resolution of four-electrode microimpedance spectra (4EMS) may provide an opportunity for routine identification of passive electrical properties for the interstitial and intracellular compartments using only interstitial access. The present study documents a structural framework in which the tissue resistivity (ρt) and reactivity (xt) that comprise spectra are computed using interstitial and intracellular microimpedance distributions that account for differences in compartment size, anisotropic electrical properties in each compartment and electrode separations. We used this framework to consider 4EMS development with relatively wide (d=1 mm) and fine (d=250 μm) electrode separations and sensors oriented along myocyte axes, across myocyte axes and intermediate between those axes.

AB0101 Articular Adipose Tissue from Osteoarthritis Patients is A Source of Cytokines and Adipokines

BackgroundRecently rheumatoid adipose tissue has been suggested to play an important role in chronic inflammatory joint diseases. Its ability to synthesize cytokines and adipokines has been characterized also in our...

The Biophysical Characteristics of Human Composite Flexor Tendon Allograft for Upper Extremity Reconstruction

Devastating volar hand injuries with significant damage to the skin and soft tissues, pulley structures and fibro-osseous sheath, flexor tendons, and volar plates pose a major problem to the reconstructive hand surgeon. Despite advances in tendon handling, operative technique, and postoperative hand rehabilitation, patients who have undergone flexor tendon reconstruction are often plagued by chronic pain, stiffness, and decreased range of motion with resultant decreased ability to work and poor quality of life. In this article, we expand the technique of human composite flexor tendon allografts (CFTAs), pioneered by Dr E.E. Peacock, Jr, which consist of both the intrasynovial and extrasynovial flexor digitorum superficialis and flexor digitorum profundus tendons and their respective fibro-osseous sheath consisting of the digital pulley structures, periosteum, and volar plates procured from cadaveric donors with the use of modern tissue processing techniques. Human cadaveric CFTAs were procured and divided into 2 groups-unprocessed CFTAs and processed CFTAs, which are cleansed and sterilized to a sterility assurance level of 10(-6). Physical length and width relationships as well as tensile strength and gliding resistance assessments were recorded pre-tissue and post-tissue processing. The histologic properties of the composite allografts were assessed before and after tissue processing. There was no significant difference with respect to physical properties of the composite allografts before or after tissue processing. The processed composite allografts demonstrated equivalent maximum load to failure and elastic modulus compared to unprocessed tendons. The gliding resistance of the composite tendon allografts was not significantly different between the 2 groups. The use of CFTAs addresses the issues of adhesion formation and lack of suitable donor material by providing a source of intrasynovial tendon in its unaltered fibro-osseous sheath without donor morbidity. This approach represents an important step toward designing an ideal material for complex flexor tendon reconstruction, which takes advantage of an intrasynovial flexor tendon in its native fibro-osseous sheath without the need for additional donor morbidity using a construct which can be engineered to have minimal tissue reactivity, negligible potential for disease transmission, and improved tendon healing properties versus standard tendon allograft.

Nestin expression and reactive phenomena in the mouse cochlea after kanamycin ototoxicity

Following injury to the adult mammalian cochlea, hair cells cannot be spontaneously replaced. Nonetheless, the postnatal cochlea contains progenitor cells, distinguished by the expression of nestin, which are able to proliferate and form neurospheres in vitro. Such resident progenitors might be endowed with reparative potential. However, to date little is known about their behaviour in situ following hair cell injury. Using adult mice and ex vivo cochlear cultures, we sought to determine whether: (i) resident cochlear progenitors respond to kanamycin ototoxicity and compensate for it; and (ii) the reparative potential of cochlear progenitors can be stimulated by the addition of growth factors. Morphological changes of cochlear tissue, expression of nestin mRNA and protein and cell proliferation were investigated in these models. Our observations show that ototoxic injury has modest effects on nestin expression and cell proliferation. On the other hand, the addition of growth factors to the injured cochlear explants induced the appearance of nestin-positive cells in the supporting cell area of the organ of Corti. The vast majority of nestin-expressing cells, however, were not proliferating. Growth factors also had a robust stimulatory effect on axonal sprouting and the proliferative response, which was more pronounced in injured cochleae. On the whole, our findings indicate that nestin expression after kanamycin ototoxicity is related to tissue reactivity rather than activation of resident progenitors attempting to replace the lost receptors. In addition, administration of growth factors significantly enhances tissue remodelling, suggesting that cochlear repair may be promoted by the exogenous application of regeneration-promoting substances.

Immunological response to bolus versus multiple injections of hylan G‐F 20 (Synvisc®) in a murine biocompatibility model

Local tissue reactivity to intra-articular injections of hyaluronic acid hylan G-F 20 (Synvisc) has been described. We used a murine biocompatibility model to study the inflammatory response to Synvisc after a single bolus injection versus the traditional three shot series of injections. Air pouches were established subcutaneously in BALB/c mice, which were injected with phosphate-buffered saline (PBS), 5 mg ultra-high molecular weight polyethylene particles (to simulate synthetic joint wear debris, positive control), 0.5 mL Synvisc (one injection/week for three weeks, harvested 14 days after last injection), or 1.5 mL Synvisc bolus (harvested either 14 or 28 days after last injection). Inflammatory gene expression and inflammation of air pouch tissue, and serum antibody titers to Synvisc were determined. Inflammation was observed with all Synvisc treatments relative to PBS (p < 0.01). However, the three injection series of Synvisc resulted in significantly (p < 0.05) greater tumor necrosis factor-alpha gene expression compared to both PBS and bolus single shot Synvisc harvested after 14 or 28 days. While all Synvisc treatments resulted in serum antibodies to Synvisc (p < 0.02 compared to PBS control group), mice that received three injections of Synvisc had higher levels than mice receiving a single injection (p < 0.01). These results demonstrate that a single bolus injection of Synvisc led to less inflammation and a lower antibody response when compared to the three-shot series of injections, supporting the current change in treatment from multiple injections to a single injection of Synvisc .

Monitoring brain functioning with evident based IT-technologies with feedback control

Scientific objectives Researches on brain functions, forming of algorithms of neuronets’ functioning and attempt of their active correction are priority in medicine. With IT medical technologies the brain function research like EEG and transcranial electro-stimulation gains new significance and should be revised. Application of methodology for clinical interpretation in the estimation of the brain bioelectric activity allows creating a universal technology for estimation and individually oriented monitoring and correction of brain functions with the purpose of improvement of neurone conductivity, reactivity of cerebral tissues to stimuli, balancing of excitation and inhibition processes [1]. Results interpretation During 17 years the Veritas Research Center has investigated sanogenic and pathological reconstructions in the brain bioelectric activity in patients of different type - from healthy to non-curable. 33% of all vascular patients were less curable (hemodynamically marked stenosises of the major arteries, combined cardiovascular insufficiency of II and III stages) and 48% of all psychoneurological patients (apallic syndrome, multiple sclerosis, lateral amyotrophic sclerosis, autism, ICP, epilepsy). The dynamics of brain bioelectric activity testified to large potential in functional activity of the brain, necessity in formation of new algorithms and IT-technologies for monitoring neurodynamics in the treatment process [2,3]. Outlook and expert recommendations Applying the IT-technology allows optimizing work of a medical staff, increase efficiency of costs on treatment due to the individually oriented approach to prediction of treatment results and active medical management on the basis of evidential medicine and monitoring of sanogenic reconstructions [2].

Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development

Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we investigate the development of these cells in second trimester human fetal tissues. MAIT cells are rare and immature in the fetal thymus, spleen and mesenteric lymph nodes. In contrast, mature IL-18Rα+ CD8αα MAIT cells are enriched in the fetal small intestine, liver and lung. Independently of localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate in response to Escherichia coli in vitro. Maturation is accompanied by the gradual post-thymic acquisition of the PLZF transcription factor and the ability to produce IFNγ and IL-22 in response to bacteria in mucosa. Thus, MAIT cells acquire innate-like antimicrobial responsiveness in mucosa before exposure to environmental microbes and the commensal microflora. Establishment of this arm of immunity before birth may help protect the newborn from a range of pathogenic microbes.

Comparison of skin closure methods in Abdominal Surgeries: Adhesive 2 – Octylcyanoacrylate/Staples/Suture Materials

The most important and necessary step in any surgical procedure is Closure of skin. Sutures and staples are the traditional methods of wound closure, while tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but they may show tissue reactivity and can require removal. Closure of wounds with staples offers the advantage of faster closure, less tissue reactivity but post-operative site pain and cost are major factors of its low acceptance. Tissue adhesives offer the advantages of no risk of needle stick injury and no requirement to remove sutures later. Tissue adhesives have better cosmetic outcome, some brands offer adhesives even with anti-bacterial (especially against Gram +ve bacilli) and anti-fungal properties so post-operative infection rate is the least with

The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions

Experiments on intrapulmonary arteries (IPAs) isolated from rats maintained in normoxia and chronic hypobaric hypoxia showed that in normoxia, the IPA contractile sensitivity to KCl was not modified by gap junction inhibition. In contrast, chronic hypoxia induced an endothelium-independent hypersensitivity, which was suppressed by gap junction inhibition. For the theoretical analysis of these results, we developed a model of interconnected myocytes. Given that smooth muscle cells in IPAs are known to communicate via gap junctions, we regard the cytoarchitecture of the IPA as a spatial network, in which nodes represent individual smooth muscle cells and the links signify intercellular communication. A single-cell model that drives the dynamics of individual nodes includes the major elements of voltage-dependent Ca(2+) signalling. In addition, interindividual variability of SMCs is introduced by distributing the reversal potentials for K(+). Cell-to-cell connection consists of passive Ca(2+) diffusion and electrical coupling, and connection between cells is determined by the topology of the intercellular network. Model predictions indicate that the experimental results can be explained by topological modifications and not by changes in the number of gap junctions. According to the model, in normoxia the myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of complexity, leading to hypersensitivity. Our results thus indicate that chronic hypoxia entails gap junction network rearrangements, leading to disturbances in the intercellular communication pathways.