Effects of anti-glaucoma medications on gangion cell survival: the DBA/2J mouse model

AbstractWe studied whether several agents, approved or undergoing trials in human glaucoma, were effective in preventing ganglion cell loss in the DBA/2J mouse. Adult DBA/2J mice were treated with timolol, pilocarpine, brimonidine, dorzolamide, or NMDA-receptor antagonist memantine. Surviving retinal ganglion cells of treated and control mice were retrogradely labeled with fluorogold and counted after whole mount preparation. In treated mice, only memantine and timolol had significant effects on retinal ganglion cell survival (P<0.0001, analysis of variance). Brimonidine was lethal to these mice, and these retinae were not analyzed further. The DBA/2J mouse represents a promising candidate for further experimentation in ocular hypertension

Checklist-based approach to measure milker behavior before and after training

So far, evaluation of training initiatives for dairy farm employees has been limited to the reaction and learning level. The effect of training on dairy farm employees' behavior has not been studied yet. The objective of this study was to determine the effectiveness of online training to change employee behavior toward best-practice routines. An interactive training course related to udder health was developed in 5 modules in Spanish and English: (1) collecting an aseptic milk sample, (2) administering intramammary treatment, (3) deciding on salable milk, (4) treating a cow at dry-off with antibiotics, and (5) administering teat sealants. Participants navigated the modules at their own pace or watched a narrated video. Employees were assessed performing 2 procedures related to dry cow treatment (i.e., treating a cow at dry-off with antibiotics, administering internal teat sealant) by using an objective structured clinical examination. If possible, all employees were scored performing the procedure on 2 cows before and within 2 to 3 wk after the training was applied

Inhaled Carbon Monoxide Provides Cerebral Cytoprotection in Pigs

Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery

Ibuprofen for neuroprotection after cerebral ischemia

ObjectiveIbuprofen has been shown to reduce cerebral ischemic injury, such as may occur after deep hypothermic circulatory arrest. We investigated whether ibuprofen has direct protective effects against excitotoxic neuronal injury, as may be seen after cerebral ischemia, by using a cell culture model.MethodsMixed cortical cultures containing neuronal and glial cells were prepared from fetal mice at 13 to 15 days gestation, plated on a layer of confluent astrocytes from 1- to 3-day-old postnatal pups. Near-pure neuronal cultures containing less than 5% astrocytes were obtained from mice of the same gestational stage. Slowly triggered excitotoxic injury was induced at 37°C by 24-hour exposure to 12.5 μmol/L N-methyl-D-aspartate or 50 μmol/L kainate. Neuronal death was quantified by release of lactate dehydrogenase from damaged cells. Data were analyzed using 1-way analysis of variance with Tukey post hoc multiple comparisons.ResultsIn mixed cultures, ibuprofen concentrations of 25 μg/mL, 50 μg/mL, and 100 μg/mL all significantly reduced N-methyl-D-aspartate–induced neuronal cell death from 74.5% to 56.1%, 38.7%, and 12.3%, respectively, revealing a strong dose response (P < .001). In near-pure cultures, ibuprofen at a concentration of 25 μg/mL failed to protect neurons, indicating that the neuroprotective effects of ibuprofen require interaction with glial cells. Furthermore, ibuprofen at 100 μg/mL was not protective against neuronal cell death induced by kainate exitotoxicity in near-pure culture but was effective in mixed cultures.ConclusionIbuprofen provides neuroprotection through glial cells against excitotoxic neuronal injury caused by glutamatergic excitotoxicity after cerebral ischemia as demonstrated by reduced neuronal cell death in mixed cell cultures. Further studies are needed to evaluate the potential of ibuprofen to reduce neurologic injury in patients experiencing an hypoxic/ischemic insult

Recomanacions per a l'entrenament i la prevenció de lesions en gimnastes de rítmica d'elit

Objectiu: Identificar els factors de risc en gimnastes de rítmica d'alt nivell i aconsellar recomanacions per prevenir el risc de lesions. Mètodes: Enquesta retrospectiva d'un any d'historial esportiu a 20 gimnastes que competien en l'àmbit nacional (mitjana d'edat, 17,1 anys; rang, 14,8-18,8 anys). Les hores d'entrenament per setmana, els minuts d'estiraments per dia i hores d'entrenament aeròbic per setmana es van analitzar com un risc potencial de factors de risc per a lesions esportives. La majoria de lesions registrades exigien deixar els entrenaments (time off); les lesions més severes (mínim de 7 dies sense activitat esportiva) eren lesions de parts blanes: tendó i/o múscul i fractures. Resultats: De les 20 gimnastes, 13 (65%) van tenir lesions que les van obligar a deixar els entrenaments i altres activitats esportives, 4 (20%) van ser lesions més severes. Van ser 17 (85%) les que van contestar que van presentar lesions musculotendinoses i 5 (25%) van patir fractures. Van ser 16 subjectes (80%) de la mostra els que van presentar lumbàlgia o fractures d'estrès lumbar, 8 amb necessitat de repòs. Una gimnasta va tenir una commoció cerebral. La regressió logística indica que l'entrenament i els estiraments, en gimnàstica rítmica estan associats a lesions de la unió musculotendinosa. En l'anàlisi multivariant es va trobar que els estiraments eren l'únic predictor independent de les lesions de la unió musculotendinosa; amb cada minut addicional es fa disminuir el risc aproximadament un 10% (p ≤ 0,01). Els exercicis d'estirament i de condicionament són els dos factors independents de predicció de fractures. El risc de fractura va ser valorat com a &gt; 60% per cada hora setmanal addicional d'entrenament (odds ratio [OR] = 1,62; p = 0,03) i minva gairebé al 20% per cada minut addicional d'estiraments diaris (OR = 0,81; p = 0,04). Cap de les variables estudiades va ser predictiva de dolor o lesió lumbar. Conclusions: Les lesions en gimnàstica rítmica es podrien reduir incrementant el temps que es dedica als estiraments per dia (almenys 40 minuts), i limitant l'entrenament a un màxim de 6 hores per setmana

Injuries and training recommendations in elite rhythmic gymnastics

Objective: To identify risk factors for injury in rhythmic sportive gymnastics and to provide recommendations for reducing the risk of injury. Methods: A one-year retrospective survey of injuries in twenty national-level rhythmic gymnasts (ages 14.8 to 18.8 years; mean age 17.1 years). Hours of rhythmic gymnastics (RG) training per week, minutes of stretching per day, and hours of conditioning per week, were analyzed as potential risk factors for injury. Main outcome measures were injuries that required time off, major injuries (at least 7 days off), injuries to muscle-tendon units, and fractures. Results: Thirteen (65%) of 20 gymnasts sustained time-loss injuries, and 4 gymnasts (20%) reported major injuries. Seventeen (85%) gymnasts reported muscle-tendon unit injuries and 5 (25%) suffered fractures. Sixteen (80%) of the gymnasts reported back pain or stress fractures of the back, 8 of whom required time off training. One gymnast (5%) incurred a concussion. Logistic regression indicated that rhythmic gymnastics training and stretching were associated with muscle-tendon unit injury. On multivariate analysis, stretching was found to be the only independent predictor of muscle-tendon unit injuries with each additional minute lowering the risk by approximately 10% (p ≥ 0.01). Conditioning and stretching were both independent predictors of fractures. The risk of fracture was estimated to increase by over 60% for each additional hour of weekly conditioning (odds ratio = 1.62; p = 0.03) and decrease by almost 20% for each additional minute of daily stretching (odds ratio = 0.81; p = 0.04). None of the variables studied were predictive of back pain or injury. Conclusions: Injuries in rhythmic gymnastics may be reduced by increasing the amount of time spent stretching per day (at least 40 minutes), and limiting conditioning to a maximum of 6 hours per week

Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation

AbstractObjective: Low-velocity and nonlaminar flow patterns in the Fontan circulation, as well as abnormal liver function in some patients, may partly account for the coagulation abnormalities seen. We examined (1) coagulation factor abnormalities before and after the Fontan procedure and (2) regional coagulation factor abnormalities in the Fontan circulation. Methods: Levels of factors V, VII, VIII, X, antithrombin III, prothrombin fragment F1+2, protein C, and protein S were measured in 2 groups of patients: In 14 patients undergoing the Fontan procedure, blood was analyzed before the operation and 5 days after the operation (group 1). The median age in this group was 3.2 years. In 10 patients who had undergone the Fontan procedure, cardiac catheterization was performed and samples were taken from the femoral vein, inferior vena cava, right atrium, and pulmonary artery (group 2). The median age in this group was 6.2 years and the median follow-up from the Fontan procedure was 4.1 years. Results: In group 1 a significant increase was noted postoperatively in the concentration of factor VIII (P < .001), factor X (P < .001), and prothrombin fraction F1+2 (P < .001). A significant decrease in the levels of antithrombin III (P < .001), protein C (P < .004), and protein S (P < .02) was also found. The increase in factors VIII and X persisted at 4 years' follow-up in group 2 patients. In group 2, no significant regional differences were observed between the coagulation factors measured at different sites. Conclusions: There is an increased tendency toward coagulation after the Fontan procedure. A prothrombotic state is supported by thrombin generation associated with reduced antithrombin III concentration. This increase in coagulation may contribute to the early and late risks of thromboembolism observed after the Fontan procedure. We did not find any regional differences in coagulation abnormalities in patients late after the Fontan procedure. Therefore, the mechanisms and causes of the coagulation abnormalities remain unclear. (J Thorac Cardiovasc Surg 2000;120:778-82

Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study

Background: The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods: We reviewed the medical records for all children with IgG level ≥2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results: After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P = 0.002), white blood cell count (P < 0.001), hemoglobin (P = 0.015), and female gender (P < 0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. Conclusions: In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP was 95% predictive of underlying autoimmune disease

Parathyroid hormone [1-34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo

SummaryObjectiveThe 1-34 amino acid segment of the parathyroid hormone (PTH [1-34]) mediates anabolic effects in chondrocytes and osteocytes. The aim of this study was to investigate whether systemic application of PTH [1-34] improves the repair of non-osteoarthritic, focal osteochondral defects in vivo.DesignStandardized cylindrical osteochondral defects were bilaterally created in the femoral trochlea of rabbits (n = 8). Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to the treatment group (n = 4) for 6 weeks, controls (n = 4) received saline. Articular cartilage repair was evaluated by macroscopic, biochemical, histological and immunohistochemical analyses. Reconstitution of the subchondral bone was assessed by micro-computed tomography. Effects of PTH [1-34] on synovial membrane, apoptosis, and expression of the PTH receptor (PTH1R) were determined.ResultsSystemic PTH [1-34] increased PTH1R expression on both, chondrocytes and osteocytes within the repair tissue. PTH [1-34] ameliorated the macro- and microscopic aspect of the cartilaginous repair tissue. It also enhanced the thickness of the subchondral bone plate and the microarchitecture of the subarticular spongiosa within the defects. No significant correlations were established between these coexistent processes. Apoptotic levels, synovial membrane, biochemical composition of the repair tissue, and type-I/II collagen immunoreactivity remained unaffected.ConclusionsPTH [1-34] emerges as a promising agent in the treatment of focal osteochondral defects as its systemic administration simultaneously stimulates articular cartilage and subchondral bone repair. Importantly, both time-dependent mechanisms of repair did not correlate significantly at this early time point and need to be followed over prolonged observation periods