1,720,980 research outputs found
Does a Prior History Predict Prolonged Recovery Times from Sports-Related Concussion in Adolescents Seen In A Specialty Clinic?
No full textPurpose: The goal of our study was to examine the effect a prior history of concussion has on clinical recovery times for adolescent patients seen in a specialty clinic for sports related concussion (SRC). Additionally, concussion clinical profiles were compared in patients with a prior history of concussion and prolonged recovery to expand empirical evidence for the therapeutic use of these profiles in specialty clinics. Hypothesis: Patients with a prior history of concussion will have similar recovery times compared to patients with no prior history of concussion. Methods: A retrospective chart review was used to identify eligible patients for analysis (n=302). A non-inferiority analysis was used to assess if patients with a history of concussion had significantly non-inferior recovery times compared to patients with no history. Chi-square analysis was used to compare clinical profiles. Exploratory analysis conducted for a small cohort (n=12) of patients who were treated for two separate concussions using within-subjects design. Results: Recovery time in patients with a history was significantly noninferior to the recovery time of patients without a history (p = 0.01). There was no association of clinical profiles across groups. The exploratory analysis revealed a non-significant decrease in recovery time across injuries, but this analysis had low power due to small sample size. Conclusion: Recovery times do not significantly increase for patients with prior history of concussion seen at a specialty clinic
Sex differences in toll like receptor 7-mediated renal injury in a murine model of autoimmune-induced hypertension
Get PDFSystemic lupus erythematosus (SLE) is a female-dominant autoimmune disease associated with hypertension. We confirmed that SLE develops later in life in male vs. female SLE mice (35 vs. [less than] 30 weeks), yet both sexes develop hypertension by 35 weeks. Renal injury is a factor in hypertensive female SLE mice only, so we aimed to investigate this latent sex difference. We hypothesized that increased toll-like receptor 7 (TLR7), an immune mediator that instigates tissue damage, promotes renal injury in female SLE mice. We found that renal cortical expression of TLR7 was indeed higher in female SLE mice. In a follow-up study we found that renal hemodynamics were impaired in female SLE mice, but not males. Our data suggest that while the hypertension in female SLE mice may be due to renal mechanisms, hypertension in males is not. Future studies will dissect sex-specific factors that should be considered when treating hypertensive patients with underlying autoimmunity
PERICYTE AND CAPILLARY MAY DECLINE DEPENDING ON THE AGING PROCESS IN MICE
No full textPurpose. In this study, we explore the effects of aging on pericytes and capillaries using mice. Pericytes are important components of the neurovascular unit and function as contractile cells around the walls of capillaries. They play many important roles in the brain, such as blood vessel formation, cerebral brain blood flow, maintenance of the blood-brain barrier, and regulation of immune cell entry into the CNS. Dysfunction of pericytes contribute to a wide range of illnesses that result in cognitive impairments such as cerebrovascular disease, stroke, Alzheimer's disease (AD), and other neurological disorders. Aging has been studied and shown to be an established risk for vascular dysfunction that affects the integrity of the neurovascular unit. Furthermore, studies have shown significant reductions in pericyte density during age-related disorders, but these studies are few. Most nutrients in the brain are supplied by capillaries, and because pericytes are embedded on capillaries, studying their patterns and effects may lead to a better understanding of the pathophysiology and preliminary triggers of age-related disorders. In this study, we explore whether both pericyte and capillary numbers are affected in the adult brain of mice as they age. Methods. All experiments were performed on young (3 month old; n=3) and old (20-23 month old; n=3) C57BL/6 male mice. To identify pericytes and capillaries for quantification, immunohistochemistry and immunofluorescence were used. Pericytes were stained using the biomarker PDGFrβ and capillaries were stained using Lectin. CA1, CA2, CA3, and DG sites were chosen for quantification in the hippocampus, and layers I-VI in the somatosensory cortex of each mouse. Confocal imaging was used to study and quantify the population of PDGFrβ and lectin-positive cells. T-tests were performed to compare the number of pericytes in the hippocampus and somatosensory cortex of the two groups of mice (young and old). Results. Old mice exhibited significantly lower capillary (via lectin) and pericyte (via PDGFrβ) numbers than young mice (p < 0.0001) in the hippocampus. There was no significant reduction in the number of pericyte (p = 0.1448) and capillary (p = 0.0967) in the somatosensory cortex. Pericytes that expressed PDGFrβ were only classified as such when colocalized to capillaries. To record the number of pericytes embedded on capillaries, the number of PDGFrβ + Lectin that expressed a "bump-on-a-log" morphology was also quantified and showed a significant reduction in the hippocampus (p < 0.0001) and somatosensory cortex (p = 0.0110) with age. Conclusion. Since cerebrovascular dysfunction plays a vital role in the development of cognitive impairment disorders, understanding the aging patterns of neurovasculature cells such as pericytes may aid in the early prevention of age-related illnesses
Analysis of Factors that affect Recruitment Process and Effectiveness of Recruitment Methods in Treatment Resistant Depression Study
No full textIntroduction: The following Research Project is a Process Improvement Study to identify the factors affecting the recruitment process and identify best recruitment method in Treatment Resistant Depression Study. Adequate recruitment is essential to any study's success. Most studies report only the effectiveness of recruitment method, but very few report the cost of randomizations. This research project will analyze the effect of different recruitment methods in the Treatment Resistant Depression Study. The study will work on cost analysis which can be critical when deciding which recruitment methods to implement in Randomized Controlled Clinical Trials. Methods: For this research project, a study will be conducted to analyze the factors that affect the recruitment process and compare the effectiveness of different recruitment methods. Factors include demographical data such as age, gender, ethnicity, race and distance from site. Data for this study will be collected from a randomized double blind, active controlled "Treatment Resistant Depression Study" conducted at North Texas Clinical Trials, Fort Worth, TX. Data will include how many subjects were consented, how many of them were enrolled and how many of them failed the screening process. Results: All four recruitment methods were compared, based on the number of subjects referred, enrolled and randomized for the study. Statistical analysis showed that there was no significant difference between subjects referred, enrolled and randomized using all four methods (p-value: 0.1920). Analysis was performed on data which showed a statistically significant difference between the number of subjects referred and randomized through subject database and clinical connection (p-value: 0.0184). Total pooled data revealed race and distance from site being the only predicting factors on the outcome of being screened into the study. II Conclusion: Patient recruitment is a vital component in assuring the success of a clinical trial and can be time consuming. One method of recruitment alone is not sufficient to meet the target enrollment. It was difficult to prove significant effect of all the factors on the recruitment process due to small sample size, but future studies with larger sample size could potentially reveal more significant impact of factors associated with the recruitment process
The Impact of Travel Stressors on the Pathogenesis of Autoimmunity in Female Lupus Mice
Get PDFPreliminary studies found that an established model of systemic lupus erythematosus, the female NZBWF1 mouse, developed heightened disease severity later in life when shipped to UNTHSC during summer due to travel stressors. We hypothesized that this was partly due to early life stress that the mice experienced, and that eliminating these stressors will attenuate disease severity. We measured biomarkers of disease severity in NZBWF1 mice that were shipped as adults and compared with mice that were shipped in early life along with mice that were not shipped at all. We found that long-term biomarkers were higher in adult travel mice compared to early life travel mice, that these biomarkers were higher in summer mice compared to winter mice, and that non-travelling mice had the highest levels. Our findings indicate that adulthood stress exacerbates disease progression in NZBWF1 mice, and that seasonal factors impacted lupus pathogenesis in these adult mice
Early Life Stress in Summer Months Accelerates the Progression of Autoimmunity in Female Lupus-Prone Mice
No full textSystemic lupus erythematosus (SLE) is an autoimmune disorder with a high prevalence of renal disease. The progression of SLE is tracked by plasma double-stranded (ds) DNA autoantibodies. We have used an established model of SLE, female NZBWF1 mice, to determine mechanisms associated with SLE-induced renal disease. Typically, mice arrive by truck from Maine at 5-6 weeks of age and are not manipulated until 30-35 weeks when renal inflammation/injury is evident. Based on anecdotal observations in different cohorts of SLE mice, we hypothesized that seasonal factors, along with the stress associated with travel in early life, accelerate disease course in aged SLE mice. We performed a retrospective analysis of 5-6 week old female NZBWF1 mice ordered between 2015-2019 and divided them into two groups based on their date of arrival: summer (April-September; n=38) and winter (October-March; n=51). Average temperature on dates of arrival was higher in summer (78.5 ± 1.8 vs. 52.5 ± 1.9 °F; p< 0.001). Plasma dsDNA autoantibodies at 34-35 weeks was higher in SLE mice that arrived in summer (6.0e5 ± 8.6e4 vs. 4.1e5 ± 5.1e4 U/mL; p=0.049) and this coincided with higher indices of renal injury in SLE mice that arrived in summer (urinary albumin: 13.3e3 ± 2.6e3 vs. 6.0e3 ± 1.5e3 ug/mL; p=0.0096). Our findings suggest early life stress compounded with seasonal factors modulate autoimmunity. Future studies will investigate biochemical processes associated with warmer temperatures and their impact on the progression of SLE-associated renal disease.Lupus Research Alliance 550778 and NIH K01HL13986
Differential effects of curcumin on renal and systemic inflammation in a mouse model of systemic lupus erythematosus
No full textResearch Appreciation Day Award Winner - 2017 Health Institute Awards, Institute for Cardiovascular and Metabolic Disease - 3rd Place Graduate Student Research AwardResearch Appreciation Day Award Winner - 2017 Texas College of Osteopathic Medicine - 2nd Place Student Research AwardResearch Appreciation Day Award Winner - 2017 Medical Student Government Association - Best in 2nd YearPurpose: The afferent vagus nerve, through its connection to the hypothalamic pituitary adrenal (HPA) axis, may help regulate inflammation by relaying inflammatory stimuli to prompt release of the anti-inflammatory hormone cortisol. Afferent vagal sensitivity may be diminished in chronic inflammatory diseases, such as systemic lupus erythematosus (SLE). SLE primarily affects reproductive age women, who commonly present with inflammatory kidney disease, diminished vagal tone, dysregulated HPA function, and inadequate basal cortisol. There is evidence that curcumin, the active compound of the spice turmeric, activates vagal afferent neurons, which may lead to increased HPA axis function and heightened cortisol release. We hypothesized that chronic curcumin administration (50mg/kg in sesame oil as vehicle; 4 weeks, daily; i.p.) would protect against chronic inflammation in the NZBWF1 mouse model of SLE by ameliorating HPA axis dysfunction.
Methods: At 30 weeks of age, female mice were designated into four groups (n = 4-5/group): SLE-CURC, SLE-VEH, CTL-CURC, and CTL-VEH. We measured splenic cytokines as endogenously released cortisol from the HPA aixis modulates activity of this immune organ.
Results: Splenic TNF-α and IL-1β expression (normalized to total protein) were increased in SLE mice compared to controls (2.57 x 107 ± 4.41 x 106 vs. 1.56 x 107 ± 1.99 x 106; p = 0.006 and 2.76 x 105 ± 9.86 x 104 vs. 3.35 x 104 ± 2.49 x 104; p = 0.020). Curcumin accentuated splenic TNF (4.85 x 107 ± 7.06 x 106; p = 0.016), while reducing splenic IL-1β in SLE mice (1.36 x 105 ± 1.74 x 104; p = 0.092). Preliminary in vitro splenocyte data support curcumin as being pro-inflammatory in SLE. Splenocytes isolated from curcumin- and vehicle-treated SLE mice released increased TNF-α when stimulated with LPS (100 ng) or norepinephrine (50 nM), (2.76 x 105 vs. 6.88 x 104 and 4.69 x 105 vs. 1.42 x 105, respectively; n = 1/group). In order to determine curcumin’s effects on kidney inflammation, we measured renal cytokine expression. SLE mice had elevated renal cortical IL-6 and TGF-β1 compared to control mice (1.27 x 105 ± 6.16 x 104 vs. 7.49 x 104 ± 1.50 x 104; p = 0.130 and 1.90 x 105 ± 7.17 x 104 vs. 7.67 x 103 ± 2.58 x 103; p = 0.006). Curcumin increased renal cortical expression of both IL-6 and TGF-β1 in SLE mice (3.37 x 105 ± 1.44 x 104 vs. 1.28 x 105 ± 6.16 x 104; p = 0.128 and 3.536 x 105 ± 1.16 x 105 vs. 1.90 x 105 ± 7.17 x 104; p = 0.152).
Conclusions: Taken together these data indicate that curcumin mostly yields pro-inflammatory effects in the setting of SLE, although its anti-inflammatory suppression of splenic IL-1β suggests a more complex interaction with the immune system. Additional studies are needed to investigate renal and cardiovascular outcomes. Further inquiry into vagal control of inflammation and the use of naturally derived compounds as an adjunct treatment of chronic inflammatory processes is warranted
Oxazolone as a Model to Induce Edema in the Lower Limb of Rats
Get PDFPurpose. Peripheral edema is a condition characterized by the accumulation of excess interstitial fluid in distal tissues and commonly manifests in the arms or legs. Untreated complex peripheral edema can progress into chronic lymphedema as impaired fluid drainage and chronic inflammation cause irreversible damage to the surrounding tissue and local lymphatics. The overall goal of our research is to study the effectiveness of osteopathic manipulative medicine techniques (OMT) for the treatment of edema, infection and inflammation. The aim of this study was to evaluate oxazolone (OXA) as a model to induce acute inflammation and lower limb edema in the rat. Specifically, we hypothesized that a single application of OXA would induce a local inflammatory response and induce edema in the lower limb. Methods. Female Sprague Dawley rats, weighing 200-250 g, were used for this study. On day 0 the right lower limb was shaved and 750 µl of 5% OXA-acetone solution or 750 µl of a 5% phosphate buffered saline (PBS)-acetone solution vehicle (VEH) was applied to the exposed skin. Lower limb measurements were made at days 0 and 6 using a Vernier caliper. At day 6, the rats were euthanized, and the bilateral hind paws were removed above the calcaneus and weighed. The spleen and bilateral inguinal lymph nodes were removed, homogenized, centrifuged and cells were stained with phycoerythrin (PE) mouse anti-rat granulocytes, fluorescein (FITC) anti-rat CD3, and allophycocyanin (APC) anti-rat CD161 antibodies. The percentage of granulocytes, T cells and dendritic cells were measured by flow cytometry. Data were analyzed by analysis of variance (ANOVA) followed by Tukey-Kramer post-test or by Student's t-test. Comparisons were made between OXA and VEH groups at day 6 post-induction. Results. OXA did not induce significant (p[greater than]0.05) changes in either hind paw thickness or hind paw volume. OXA significantly (P[less than]0.05) increased the concentration of macrophages, neutrophils, and dendritic cells, and T cells within inguinal lymph nodes. Conclusions. OXA induced an acute local inflammatory response in the draining inguinal lymph nodes. However, as used in this approach, OXA did not induce peripheral edema. In future studies we will investigate alternate strategies to induce lower limb edema in the rat
The impact of early life stressors on the progression of SLE
No full textOur preliminary studies show that an established model of systemic lupus erythematosus (SLE), the female NZBWF1 mouse, had worsened indices of disease later in life when the mice were shipped to our institution at an early age during the summer. We hypothesized that interleukin (IL)-6-induced release of heat shock protein 90 (HSP90) is upregulated in response to this summer early-life stressor, thus accelerating autoimmunity and renal disease in female SLE mice. To begin to study this, we measured renal IL-6 and HSP90 in 6-week-old female NZBWF1 mice that were shipped in winter or summer months and found that both were elevated immediately following summer compared to winter travel. Our findings indicate that the mediators associated with early-life travel/seasonal stressors may predict the progression of autoimmunity in SLE-prone mice. Other findings here within highlight the specificity of this effect in the kidney and describe sex differences in the observed phenomena
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