Testosterone Inhibits Migration of Porcine Coronary Smooth Muscle Cells via PKC [abstract]

Abstract only availableFaculty Mentor: Doug Bowles, Veterinary Biomedical SciencesMigration of smooth muscle cells from the media into the intima has been shown to play a significant role in atherosclerosis. Recent clinical trials of atherosclerosis indicate that testosterone (TST) protects against coronary heart disease, however, the role of TST in coronary smooth muscle (CSM) migration has not been determined. We tested the hypothesis that TST inhibits migration of CSM. Cultured subconfluent (dedifferentiated) and 6 day serum starved postconfluent (differentiated) porcine CSM from passages 2 to 6 were plated in 8μm pore, 96 well, chemotaxis plates (Millipore). Migration was stimulated by the addition of growth factor PDGF-BB (30ng/ml) for 4 hours in the presence and absence of 1nM, 20nM and 100nM TST. In both dedifferentiated and differentiated cells, TST inhibited migration at all concentrations in a dose-dependent manner (60, 85 and 90 % inhibition respectively). Chelerythrine (1μM), a PKC-specific inhibitor, completely blocked migration by TST. In differentiated cells, 18 hour pretreatment with TST showed similar inhibition. Our data demonstrate that TST inhibits CSM migration through a PKC-dependent mechanism. Supported by HL071574 and NASA.NASA; National Institute of Healt

Closed reduction and percutaneous intramedullary pinning of displaced radial neck fracture in a 12 years old child: reduction technique and outcome

Fracture of the radial neck are uncommon injuries in the pediatric age group. In children, they may present as radial neck fractures, a component of forearm fracture-dislocations, or as isolated fracture-dislocations. Most of the displaced radial neck fractures with more than 300 angulations (Judet type III and IV fractures) should be surgically treated. An unusual variant of radial neck fracture with dislocation of the radial head to the radial side without associated nerve injury. The fracture-dislocation was fixed with closed reduction and Kirschner wire under image intensifier. The patient is being followed up for 6 months. Operative treatment with closed reduction and intramedullary pinning has better correction of angulation and rotation compared to closed reduction techniques with angulation of 300 or more with 100 of rotation. we achieved a supination of 800 and a pronation of 500

Mast cells and the IL-33/ST2 axis are essential determinants of carbon nanotube toxicity

The rise of nanomaterial use in a variety of applications, including biomedical imaging and drug delivery, has led to concern about the potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions, including pulmonary and cardiovascular diseases. Mast cells are well known to act in response to danger signals through a variety of receptors and pathways including IL-33 and the IL-1 like receptor ST2. The aim of this study was to investigate involvement of mast cells and the IL-33/ST2 axis in the pulmonary and cardiovascular toxicities induced by engineered multi-walled carbon nanotubes (MWCNTs) following oropharyngeal aspiration. We assessed inflammatory, fibrotic, and functional responses in the lung, as well as cardiac ischemia-reperfusion (IR) injury responses in C57BL/6, Kit W-sh (mast cell deficient), Kit W-sh reconstituted with either wild-type or ST2 mast cells, and ST2 deficient mice. Mice with a sufficient population of mast cells (C57BL/6 and reconstituted Kit W-sh mice) exhibited significant pulmonary inflammation, exhibited by increased neutrophils and associated with elevated IL-33, impaired pulmonary function, increased granuloma formation, and collagen deposition 30 days following exposure to MWCNT. Additionally, exacerbation of myocardial infarction was observed in the same groups of mice 1 day following MWCNT exposure. These toxicological effects of MWCNTs were observed only in mice with a sufficient population of mast cells and were not observed when mast cells were absent or incapable of responding to IL-33 (Kit W-sh, Kit W-sh reconstituted with ST2 mast cells or ST2 mice). These findings establish for the first time, an unrecognized, but critical role for mast cells and the IL-33/ST2 axis in orchestrating adverse pulmonary and cardiovascular responses to an engineered nanomaterial, giving insight into a previously unknown mechanism of toxicity. In identifying the importance of the IL-33/ST2 axis and mast cells in this novel mechanism of toxicity, our study provides a means of addressing current concerns regarding nanoparticle exposures and the safety of engineered nanomaterials for use in biomedical applications in identifying a realistic therapeutic target for potential nanoparticle induced toxicities.Ph.D

Spectrophotometric assay of immobilized tannase

A procedure for the assay of immobilized tannase with Polyacrylamide gel, collagen and Duolite-S-762 as matrices is described. It is based on the spectrophotometric determination of gallic acid formed by the enzymatic hydrolysis of tannic acid. The kinetic parameters of the enzymatic reaction have been studied and an assay procedure has been formulated. This method appears to be much more accurate than those reported earlier

The Intensity of Childhood Trauma Has No Impact on The Cognitive Development of Decision-Making Style to be Exhibited in Adulthood

The literature clearly shows that childhood experiences, specifically those of trauma, have an impact on cognitive development. However, it remains unclear exactly how trauma influences the way in which high order cognitive processes, including decision-making are manifested in adulthood. Improving our understanding of the role childhood trauma has in the development of specific cognitive processes will aid in developing improved interventions and practices in the realm of childhood trauma. Here we investigated the relationship between intensity of childhood trauma, age of traumatic event, intensity of confiding in someone at the time of the traumatic event, and general decision-making style in adulthood. Participants completed the childhood traumatic events scale (CTES; Pennebaker & Susman, 2013), and decision-making style in adulthood (GDMS; Scott & Bruce, 1995). Intuitive decision-making style was most frequently seen, however no significant effect of intensity of childhood trauma, age, confiding on decision-making style in adulthood was observed. These findings indicate that intensity of childhood trauma may not impact the way in which decision-making develops

CVD and COVID-19: Emerging Roles of Cardiac Fibroblasts and Myofibroblasts

Cardiovascular disease (CVD) is the leading cause of death worldwide. Current data suggest that patients with cardiovascular diseases experience more serious complications with coronavirus disease-19 (COVID-19) than those without CVD. In addition, severe COVID-19 appears to cause acute cardiac injury, as well as long-term adverse remodeling of heart tissue. Cardiac fibroblasts and myofibroblasts, being crucial in response to injury, may play a pivotal role in both contributing to and healing COVID-19-induced cardiac injury. The role of cardiac myofibroblasts in cardiac fibrosis has been well-established in the literature for decades. However, with the emergence of the novel coronavirus SARS-CoV-2, new cardiac complications are arising. Bursts of inflammatory cytokines and upregulation of TGF-β1 and angiotensin (AngII) are common in severe COVID-19 patients. Cytokines, TGF-β1, and Ang II can induce cardiac fibroblast differentiation, potentially leading to fibrosis. This review details the key information concerning the role of cardiac myofibroblasts in CVD and COVID-19 complications. Additionally, new factors including controlling ACE2 expression and microRNA regulation are explored as promising treatments for both COVID-19 and CVD. Further understanding of this topic may provide insight into the long-term cardiac manifestations of the COVID-19 pandemic and ways to mitigate its negative effects

Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

<p>Abstract</p> <p>Background</p> <p>Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.</p> <p>Methods</p> <p>MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.</p> <p>Results</p> <p>Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.</p> <p>Conclusions</p> <p>These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.</p

Are There Limitations to Exercise Benefits in Peripheral Arterial Disease?

Substantial evidence exists indicating that inactivity contributes to the progression of chronic disease, and conversely, that regular physical activity can both prevent the onset of disease as well as delay the progression of existing disease. To that end “exercise as medicine” has been advocated in the broad context as general medical care, but also in the specific context as a therapeutic, to be considered in much the same way as other drugs. As there are non-responders to many medications, there also are non-responders to exercise; individual who participate but do not demonstrate appreciable improvement/benefit. In some settings, the stress induced by exercise may aggravate an underlying condition, rather than attenuate chronic disease. As personalized medicine evolves with ready access to genetic information, so too will the incorporation of exercise in the context of those individual genetics. The focus of this brief review is to distinguish between the inherent capacity to perform, as compared to adaptive response to active exercise training in relation to cardiovascular health and peripheral arterial disease