1997 research outputs found
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Evaluation of hypoglycemia resulting from hyperglycemic clamps
No full textHyperglycemic clamps are used as a gold standard measurement of beta cell function, allowing for measurement of a biphasic insulin response. Under this technique, the plasma glucose concentration is raised to a target concentration of 200 mg/dL by exogenous infusion of dextrose. The target glucose concentration is sustained by regular titration of the dextrose infusion rate. An adverse event commonly associated with hyperinsulinemic clamps or arginine infusions is post-clamp hypoglycemia (blood glu-cose \u3c60mg/dL). However, hyperglycemic clamp testing of nondiabetic individuals has not traditionally been associated with this outcome. In a recent study of beta cell function in nondiabetic individuals at genetic risk for type 1 diabetes and unrelated controls, we observed hypoglycemia in 11/67 clamps post discontinuation of dextrose infusion. We hypothesized that demographic or clamp related factors may be associated with hypoglycemia in the 60 minutes after discontinuation of dextrose infusion. Three non-diabetic populations were analyzed: islet Ab negative first-degree relatives of T1D pro-bands (n=19), Ab positive relatives of T1D probands (n=5), and healthy controls with no family history of T1D and undetectable Abs (n=15). Demographic factors (study group, age, BMI, sex, HbA1c, fasting glucose) and clamp factors (average glucose infusion rate during the clamp, maximum glucose infusion rate during the clamp, urine glucose, and urine volume) were compared among those who became hypoglycemic and those who did not. Intraindividual variability of post clamp hypoglycemia was also evaluated in those who had two clamp visits (n=27). Ten (25.64%) participants exhibit-ed hypoglycemia (average glucose of 50.97 mg/dL) in at least one clamp visit and 29 (74.36%) were normoglycemic (average glucose of 81.07 mg/dL) during the 60 minutes after discontinuation of dextrose. No differences were present in rates of hypoglycemia between participant groups. The mean HbA1c (5.009%) of participants who developed hypoglycemia post-clamp was lower than the mean HbA1c (5.195%) for participants who were normoglycemic after the clamp (p value=0.0403), however absolute differences were small and significant overlap existed between both groups. We did not detect significant differences between hypoglycemic and normoglycemic participants for any other demographic or clamp factors analyzed. With regards to patients with 2 available clamp visits, of the 8 subjects who developed hypoglycemia, only one experienced it during both visits. Hypoglycemia is not uncommon after hyperglycemic clamp testing. Hyperglycemic clamp testing should include universal post-clamp glucose monitoring, as no clear demographic factors could be used to identify risk of hypoglycemia
Indixanol contrast medium partially separates infectious strains of Candida into persister and non-persister populations
No full textCandida albicans and Candida glabrata, are two clinically relevant strains of yeast. They make up a majority of commonly seen pathologies such as vaginal yeast infections, nosocomial infections, and infections of immunocompromised patients. Candida stains can form perisiter colonies, which have reduced metabolic activity and increased resistance to antifungal treatment. Observing survival after a heat challenge provides a method for demonstrating the persister state among yeast and allows investigation of environmental conditions that increase or decrease the persistership of a microbial culture. Persisters are also resistant to antifungals like Amphotericin. It has been demonstrated that Saccharomyces could be separated into perisiter and non-persister populations by centrifuging a culture atop a 30% indixanol density cushion. The applicability of this technique to the more clinically relevant Candida albicans became the principal aim of this study. The indixanol separation, following assiduously the reported protocol, was applied to two strains of C. albicans as well as one C. glabrata. The protocol for Saccharomyces used 7 day-old cultures to enhance the number of persisters. In our hands, most of the organisms were found in the pellet, which was purported to be the persister portion of the population. Flow cytometry was used to quantify the percent of the culture found in the upper versus the pellet layer. Viability demonstrated by growth on agar plates following heat treatment revealed that vegetative cells were found in both layers, but most vegetative cells remained in the upper layer. Amphoteri-cin B treatment for 30 minutes followed by heat treatment reduced the number of per-sisters. A shorter growth time (2 days increased the number of vegetative cells and substantially reduced the size of the pellet. Conclusion: This method provides an incomplete separation of persisters and vegetative cells but may have utility in screening compounds for anti-persister activity
Effects of Aging on Skeletal Muscle Hypertrophy
No full textContext: Skeletal muscle is essential for proper bodily functions by playing key roles in strength and movement, and it accounts for roughly 50% of our total body mass. Decreases in total muscle mass or mass-specific function would be expected to have a magnified negative impact. Sarcopenia, an age-dependent loss of motor nerves, leading by necessity to a coincident loss of muscle mass, would have exactly this kind of effect. Results: This age-dependent disorder may be the result of aberrant mTOR signaling, irregular miRNAs content, malnutrition and lack of activity, and age-related inflammation. It may be possible to reduce the effects of sarcopenia via strength training, as well as increasing daily intakes of protein, essential amino acids, and fish oils. Combining the consumption of whey protein, which is high in leucine, and poly-unsaturated fatty acids with strength training resulted in increases in muscle mass and strength. Objective: This review examines the existing causes and effects of age-related sarcopenia, as well as methods that might ameliorate problems associated with age-related sarcopenia
Bone-derived Sclerostin has endocrine actions in adipocyte precursors and pancreatic beta-cells
No full textOsteocyte (Ot)-derived Sclerostin (Scl) has local actions in bone mediated by Lrp 4/5/6 receptors, inhibiting bone formation and stimulating bone resorption by antagonizing Wnt signaling. Emerging evidence suggests that Scl also exerts functions in distant tissues. We report here that mice with activated β-catenin in Ots (daβcatOt) and mice lacking Lrp4 in Ots (Lrp4Ot), two different genetic mouse models that exhibit high se-rum Scl, display a 2-fold increase in whole-body fat and peripheral white (WAT) and brown (BAT) adipose tissue mass. The goal of this study was to determine the contribution of Ot-derived Scl to the regulation of peripheral fat mass and glucose metabolism. To determine Scl’s contribution to the high fat phenotype, daβcatOt mice were crossed with SOST knockout mice. Deletion of SOST restored to control levels the elevated body-fat mass and WAT mass, but not BAT, in daβcatOt mice. In contrast, blockade of Scl signaling in bone via genetic deletion of Lrp4 in Ots, did not alter the elevated body fat displayed by daβcatOt mice, demonstrating that Scl actions on adi-pose tissue were not mediated by Scl actions on Ots. Consistent with direct effects of Scl on adipose tissue, treatment with recombinant Scl enhanced by 20% adipogenic differentiation of murine adipocyte precursors (preAd) in vitro, and increased the expression of mitochondrial related genes Pgc1a, Ucp1, and Prdm16 in preAds as well as in ex vivo fat organ cultures established from WAT. Further, Scl augmented mitochondrial respiration in preAds by inducing a 15% increase in maximal respiration and spare capacity, suggesting that Scl promotes adipogenesis in preAds by regulating mitochondrial oxidative phosphorylation. Both models of high serum Scl, daβcatOt and LRP4Ot mice, also were hypoglycemic and exhibited impaired glucose tolerance com-pared to control littermates. Genetic deletion of SOST restored to control values the glucose levels in blood and glucose tolerance, showing that serum Scl regulates glucose metabolism. Further, Scl fully prevented the increase in insulin mRNA expression induced by Wnt3a in rat pancreatic β-cells and decreased by 45% insulin secretion induced by high-glucose media, demonstrating that Scl acts directly on pancreatic β-cells to impair insulin production. In concert, these findings demonstrate that Scl exerts endocrine actions in fat tissues and the pancreas to regulate body composition and glucose metabolism, respectively. Further, our results provide new evidence supporting that endocrine actions of Scl mediate the crosstalk between bone and fat and the pancreas
Comparison of Human Cytokine Array, Cytokine Bead Arrays, and Protein ELISA in determining cytokine production in media supernatant from in vitro strain of human dermal fibroblasts
Get PDFThis experiment analyzes three different techniques used in literature to detect cytokine release from cells in vitro: the Human Cytokine Array (HCA) by R&D Systems, the BD Cytometric Bead Array (CBA) assay, and protein enzyme-linked immunosorbent assay (ELISA). The model used to test these assays was a human dermal fibroblast cell culture that was subjected to strain profiles by the Flexcell FX-6000 that include a repetitive motion injury, a profile with the injury strain as well as a strain representing myofascial release, and a control that was not strained. Each of these techniques analyzed the conditioned media of the cultures collected 96 hours after the strain profile was completed. The HCA was proficient at analyzing a large amount of cytokines at once, though was less sensitive than the other assays. The CBA measured six cytokines at once and showed high sensitivity in detecting differing concentrations in the conditioned media. The ELISA could only measure one cytokine at a time, but also showed high sensitivity in detecting differing concentrations in the conditioned media. This experiment also looked at the cost and amount of sample used. This experiment also considers price, amount of sample used and duration of the assay to determine ideal situations to use each technique
The American Catholic Church Censors the Movies
Get PDFTraces the rise of the movie industry from its raffish nickelodeon roots in the late nineteenth century to enormous popularity in the first half of the twentieth century. Self-censorship by the movie industry to satisfy its moralist critics having failed, Hollywood found it in its interests to use Catholics to censor those motion pictures the Church judged dangerous to souls. That effort was a double-barreled one: Faced with having to comply with expensive and diverse demands from city and state censorship boards to delete scenes, in 1930 the movie industry accepted an elaborate prescriptive film code, written by a Jesuit monsignor, describing what could and could not be shown and said. For the first four years enforcement was lacking, but by 1934, the Production Code Administration (PCA), led by an energetic Catholic layman and his staff, was empowered to scrutinize a film’s theme, script, language, costuming, etc., at every step of the process. Movie producers had to negotiate with the PCA to earn a Seal, evidence that the movies would not undermine the morals of its patrons.
The second barrel was the Legion of Decency, in which a group of Catholic women in New York, members of the International Federation of Catholic Alumnae, (IFCA), led by a priest, served as a second jury with its own processes; it identified films acceptable for all audiences from children to adult, with the morally objectionable for particular groups identified and those unsuitable for any audience condemned. A special feature of the Legion’s influence was the widespread practice of the laity’s yearly recitation of a pledge at Mass promising to avoid all condemned movies and the theaters which showed them, a promise which many laity believed, mistakenly, that to disobey constituted a mortal sin.
The heyday of the effectiveness of the PCA and the Legion lasted from 1934 to the mid-1950s when movie producers and the movie audience began to resist. By 1949, Hollywood, facing an existential threat from television, had to provide what “the box” could not--blockbuster epics, technicolor, 3-Dimensional, drive-in theaters--all would be tried, but the quickest path to successfully compete was more boundary-breaking motion pictures, especially sex and crime. Television was only one of the industry’s problems. Inevitably, for good reasons and bad, what the public wanted affected the social mores and were reflected on the movie screen. Whatever the 1950s may have lacked, the American people were more sophisticated and confident than the Great Depression generation had been, and the movie audience for more realistic, cerebral, and artistic movie fare had grown.
Two Catholic movie critics are featured: the convert, William H. Mooring, syndicated columnist for Tidings, the Los Angeles archdiocesan newspaper, and James W. Arnold, syndicated in the Indianapolis archdiocesan paper, Marquette University associate professor in journalism, and self-described “movie nut.” Mooring, the older man, was especially wary about the dangers of communism in the movies and in real life in postwar World War II America, while Arnold’s habit was to find reasons to praise the films of the 1960s and 1970’s he reviewed.
To illustrate the issues involved and the changes over time in the PCA and Legion of Decency rulings, a number of films are given extended discussion, among them, “She Done Him Wrong,” 1933, “The Farmer’s Daughter,” 1947, “The Miracle,” 1950, “The Outlaw,” 1943, “The Streetcar Named Desire, 1951, “The French Line,” 1953, “The Moon is Blue,” 1953, “Martin Luther, 1953, “La Dolce Vita,” 1960, “The Pawnbroker,” 1965, “Bonnie and Clyde,” 1967, and “Midnight Cowboy,” 1968.
The appendices include discussions of Catholics and censorship in other media--books, the comics, political films, documentaries, television, religious films, and the stage
Developing an in vitro model of CKD-MBD induced αKlotho suppression
No full textChronic Kidney Disease (CKD) affects approximately 1 in 10 Americans. Diabetic nephropathy is also associated with the development of chronic kidney disease-mineral bone disorder (CKD-MBD). CKD-MBD disrupts the normal bone-kidney endocrine axis responsible for regulating mineral metabolism, and hyperphosphatemia develops in late stage disease. Important clinical hallmarks of the CKD-MBD progression include elevated bioactive bone derived Fibroblast growth factor-23 (FGF23) and suppression of FGF23’s co-receptor, αKlotho (αKL). In healthy individuals the hormone FGF23, primarily produced by bone, and αKL aid in maintaining normal phosphate and vitamin D homeostasis. It is currently unknown what drives the suppression of αKL expression, however increasing αKL expression in CKD-MBD models is being investigated as a novel therapeutic. Our study sought to develop a novel in vitro model of one of the clinical hallmarks of the progression of CKD-MBD, αKL suppression, to investigate both possible stimuli of its repression and downstream signaling events. The Human Embryonic Kidney (HEK) cell line was used to determine if changes in fluid shear stress, similar to those that occur in diabetic nephropathy, could lead to reduced αKL expression. HEK cells were plated and exposed to oscillatory fluid shear stress (OFSS) for intervals between 0-60 min to examine protein expression or 0-2 hours to assess gene expression. HEK cells were sensitive to mechanical stimulation as pathways including increased ERK phosphorylation occurred in response to OFSS. In response to longer bouts of OFSS αKL expression was reduced. Dramatic changes in fluid shear stress may serve as a stimulus for reduced αKL expression in CKD-MBD. Further studies are underway to investigate downstream signaling events related to αKL suppression. Understanding both the stimuli of αKL suppression and related downstream signaling events could provide novel therapeutic targets for the treatment of CKD-MBD
Congestive Heart Failure--Experience in OPTIMISTIC facilities
No full textThis project, OPTIMISTIC, is a retrospective study that focuses on Congestive Heart Failure(CHF) in Indiana Nursing homes. The purpose of the study was to find better ways in which to implement in house care to these CHF patients rather than transferring them to the hospital. There were a variety of data analytics tools, primarily IU REDCAP, uses to pull charts from the OPTIMISTIC nursing homes in Indiana. Five of the nursing homes were selected and used for this study. All five nursing homes were travelled to and the on-campus charts were reviewed as well as any online charts they used in their facilities. A data collection tool was used to collect specific data for each patient that was used in the study. The results indicated that while CHF is a very hard disease to manage the Nursing homes were doing an adequate job of treating them in house. 53.3 % of the patients returned to pre-certification condition and remained in the nursing home. Most nursing homes in the study followed the OPTIMISTIC program in which they were prescribing a diuretic as the first line agent. In conclusion, the OPTIMSITC program is decreasing hospital transfers within the Indiana nursing homes as well as saving health care dollars. In the future focusing a research project on the art of charting a patient in a medical database could be very helpful. The discrepancies between the nursing home charts brought forward a major problem in the medical industry as a whole
3D Visualization of Pancreatitis: New Approaches for Diagnosis
No full text3D visualization research is useful as a learning tool for medical students learning human anatomy and as a diagnostic tool for practicing physicians. Here we explore the use of this application of medical imaging in recognizing pancreatic cancer. One important problem is that pancreatic cancer is most commonly diagnosed in later stages which leads to a poor prognosis for survival. Pancreatitis presents with indistinct upper gastrointestinal symptoms, making it sometimes difficult to diagnose in clinical examination. The difficulty of early diagnosis and possible application of 3D visualization to the problem is the focus of our study. Using 3D imaging methods, we present the anatomy of the pancreas, pathologies related to pancreatic cancer, and comment on why it is so often unrecognized or misdiagnosed. The pancreas can be difficult to view, even by trained physicians and technicians. 3D imaging allows students to practice visualizing the pancreas in the same format they will with a future patient. Anonymized CT scans were obtained of a healthy patient and a patient with pancreatitis. Amira Software, a 3D imaging analytical tool, was used to measure structural density and generate an outline for research. Using Amira, we interpolated the 2D image and provided a 3D image for analysis and comparison between the healthy and unhealthy pancreas. Several surrounding organs were generated to help ascertain size and location of the pancreas. The result of this project is that the pancreas is not always well visualized with CT technology and could possibly be overlooked, even by a well-practiced physician. Different techniques should be utilized and taught to medical students to help in the early detection of pancreatic diseases