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In vitro model suggests oxidative stress involved in keratoconus disease
Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype
Protein Pattern Formation
Protein pattern formation is essential for the spatial organization of many
intracellular processes like cell division, flagellum positioning, and
chemotaxis. A prominent example of intracellular patterns are the oscillatory
pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological
function is to ensure precise cell division. Cell polarization, a prerequisite
for processes such as stem cell differentiation and cell polarity in yeast, is
also mediated by a diffusion-reaction process. More generally, these functional
modules of cells serve as model systems for self-organization, one of the core
principles of life. Under which conditions spatio-temporal patterns emerge, and
how these patterns are regulated by biochemical and geometrical factors are
major aspects of current research. Here we review recent theoretical and
experimental advances in the field of intracellular pattern formation, focusing
on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl
Eccentric lamellar keratolimbal grafts harvested with a manually guided microkeratome
Background: To perform lamellar keratolimbal allograft transplantation in a one- step procedure with a single graft, we investigated the feasibility of harvesting eccentric lamellar keratolimbal grafts from conventionally processed corneoscleral buttons using a manually guided microkeratome in conjunction with an artificial anterior chamber system. Methods: We used the Moria LSK- One microkeratome and the automated lamellar therapeutic keratoplasty ( ALTK) system ( Antony, France). Ten human donor eyes were used to obtain single- piece lamellar keratolimbal grafts. Specimens were processed for light and electron microscopy. Results: Eccentric keratolimbal grafts could be obtained from all human donor buttons. Grafts include a crescent- shaped limbal and a large corneal portion. No visible damage to the limbal region was discernible. Conclusion: Our data show that the LSK- One microkeratome in conjunction with the ALTK system allows harvesting eccentric keratolimbal grafts from donor corneoscleral buttons. Copyright (c) 2007 S. Karger AG, Basel
Muscular dysfunction elicited by creep of lumbar viscoelastic tissues.
Abstract The biomechanics, histology and electromyography of the lumbar viscoelastic tissues and multifidus muscles of the in vivo feline were investigated during 20 min of static as well as cyclic flexion under load control and during 7 h of rest following the flexion. It was shown that the creep developed in the viscoelastic tissues during the 20 min of static or cyclic flexion did not fully recover over the 7 h of following rest. It was further seen that a neuromuscular disorder with five distinct components developed during and after the static and cyclic flexion. The neuromuscular disorder consisted of a decreasing magnitude of reflexive EMG from the multifidus upon flexion as well as of superimposed spasms. The recovery period was characterized by an initial muscle hyperexcitability, a slowly increasing reflexive EMG and a delayed hyperexcitability. Histological data from the supraspinous ligament demonstrate significant increase (× 10) in neutrophil density in the ligament 2 h into the recovery and even larger increase (×100) 6 h into the recovery from the 20 min flexion, indicating an acute soft tissue inflammation. It was concluded that sustained static or cyclic loading of lumbar viscoelastic tissues may cause micro-damage in the collagen structure, which in turn reflexively elicit spasms in the multifidus as well as hyperexcitability early in the recovery when the majority of the creep recovers. The micro-damage, however, results in the time dependent development of inflammation. In all cases, the spasms, initial and delayed hyperexcitabilities represent increased muscular forces applied across the intervertebral joints in an attempt to limit the range of motion and unload the viscoelastic tissues in order to prevent further damage and to promote healing. It is suggested that a significant insight is gained as to the development and implications of a common idiopathic low back disorder as well as to the development of cumulative trauma disorders
A rare presentation of Pulmonary Lymphangitic Carcinomatosis in cancer of lip: case report
Squamous cell carcinoma of lip is a common malignancy in Indian subcontinent. Metastatic spread is infrequent. Although advanced tumours spread to lymph nodes in the neck, it does not typically present with lung metastasis or with lymphangitic carcinomatosis. We describe a patient who developed cough and increasing dyspnoea while on treatment for carcinoma of lip. Chest x-ray and computed tomography were consistent with lymphangitic carcinomatosis. Lymphangitic carcinomatosis occurs with many different primary tumours and can rarely occur in oral cancers. This is the first report from carcinoma of lip
Younger age of escalation of cardiovascular risk factors in Asian Indian subjects
<p>Abstract</p> <p>Background</p> <p>Cardiovascular risk factors start early, track through the young age and manifest in middle age in most societies. We conducted epidemiological studies to determine prevalence and age-specific trends in cardiovascular risk factors among adolescent and young urban Asian Indians.</p> <p>Methods</p> <p>Population based epidemiological studies to identify cardiovascular risk factors were performed in North India in 1999–2002. We evaluated major risk factors-smoking or tobacco use, obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre-specified definitions in 2051 subjects (male 1009, female 1042) aged 15–39 years of age. Age-stratified analyses were performed and significance of trends determined using regression analyses for numerical variables and Χ<sup>2 </sup>test for trend for categorical variables. Logistic regression was used to identify univariate and multivariate odds ratios (OR) for correlation of age and risk factors.</p> <p>Results</p> <p>In males and females respectively, smoking or tobacco use was observed in 200 (11.8%) and 18 (1.4%), overweight or obesity (body mass index, BMI ≥ 25 kg/m<sup>2</sup>) in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9, females > 0.8) in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL cholesterol (≥ 130 mg/dl) in 9.4% and 8.9%, low HDL cholesterol (<40 mg/dl males, <50 mg/dl females) in 16.2% and 49.7%, hypertriglyceridemia (≥ 150 mg/dl) in 9.7% and 6%, diabetes in 1.0% and 0.4% and the metabolic syndrome in 3.4% and 3.6%. Significantly increasing trends with age for indices of obesity (BMI, waist, WHR), glycemia (fasting glucose, metabolic syndrome) and lipids (cholesterol, LDL cholesterol, HDL cholesterol) were observed (p for trend < 0.01). At age 15–19 years the prevalence (%) of risk factors in males and females, respectively, was overweight/obesity in 7.6, 8.8; high WHR 4.9, 14.4; hypertension 2.3, 0.3; high LDL cholesterol 2.4, 3.2; high triglycerides 3.0, 3.2; low HDL cholesterol 8.0, 45.3; high total:HDL ratio 3.7, 4.7, diabetes 0.0 and metabolic syndrome in 0.0, 0.2 percent. At age groups 20–29 years in males and females, ORs were, for smoking 5.3, 1.0; obesity 1.6, 0.8; truncal obesity 4.5, 3.1; hypertension 2.6, 4.8; high LDL cholesterol 6.4, 1.8; high triglycerides 3.7, 0.9; low HDL cholesterol 2.4, 0.8; high total:HDL cholesterol 1.6, 1.0; diabetes 4.0, 1.0; and metabolic syndrome 37.7, 5.7 (p < 0.05 for some). At age 30–39, ORs were- smoking 16.0, 6.3; overweight 7.1, 11.3; truncal obesity 21.1, 17.2; hypertension 13.0, 64.0; high LDL cholesterol 27.4, 19.5; high triglycerides 24.2, 10.0; low HDL cholesterol 15.8, 14.1; high total:HDL cholesterol 37.9, 6.10; diabetes 50.7, 17.4; and metabolic syndrome 168.5, 146.2 (p < 0.01 for all parameters). Multivariate adjustment for BMI, waist size and WHR in men and women aged 30–39 years resulted in attenuation of ORs for hypertension and dyslipidemias.</p> <p>Conclusion</p> <p>Low prevalence of multiple cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and metabolic syndrome) in adolescents and rapid escalation of these risk factors by age of 30–39 years is noted in urban Asian Indians. Interventions should focus on these individuals.</p
After-hours colorectal surgery: a risk factor for anastomotic leakage
__Purpose:__ This study aims to increase knowledge of colorectal anastomotic leakage by performing an incidence study and risk factor analysis with new potential risk factors in a Dutch tertiary referral center.
__Methods:__ All patients whom received a primary colorectal anastomosis between 1997 and 2007 were selected by means of operation codes. Patient records were studied for population description and risk factor analysis.
__Results:__ In total 739 patients were included. Anastomotic leakage (AL) occurred in 64 (8.7%) patients of whom nine (14.1%) died. Median interval between operation and diagnosis was 8 days. The risk for AL was higher as the anastomoses were constructed more distally (p = 0.019). Univariate analysis showed duration of surgery (p = 0.038), BMI (p = 0.001), time of surgery (p = 0.029), prophylactic drainage (p = 0.006) and time under anesthesia (p = 0.012) to be associated to AL. Multivariate analysis showed BMI greater than 30 kg/m2(p = 0.006; OR 2.6 CI 1.3-5.2) and "after hours" construction of an anastomosis (p = 0.030; OR 2.2 CI 1.1-4.5) to be independent risk factors.
__Conclusion:__ BMI greater than 30 kg/m2and "after hours" construction of an anastomosis were independent risk factors for colorectal anastomotic leakage
Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice
The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health
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