724 research outputs found
PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet
Summary : We evaluated the effects of parathyroid hormone (PTH), pamidronate, or renutrition on osseointegration of titanium implants in the proximal tibia of rats subject to prolonged low-protein diets. PTH improved mechanical fixation, microarchitecture, and increased pull-out strength. Pamidronate or renutrition had lesser effects. PTH can thus improve implant osseointegration in protein-malnourished rats. Introduction: Protein malnutrition impairs implant osseointegration in rats. PTH and pamidronate prevent deleterious effects of protein restriction introduced just prior to implantation. Whether these treatments improve osseointegration after chronic protein deprivation, i.e., in osteopenic bone at time of implantation, is unknown. We evaluated effects of PTH, pamidronate, or renutrition on resistance to pull-out of titanium rods implanted into the rat tibiae following isocaloric low-protein intake. Methods: Forty-one adult female rats received normal or isocaloric low-protein diets. Six weeks later, implants were surgically inserted into proximal tibiae. Following implantation, rats on low-protein diets were treated with PTH (1-34), pamidronate, saline vehicle, or normal protein diets, for another 8weeks. Tibiae were removed for micro-computerised tomographic morphometry and evaluation of pull-out strength. Results: Pull-out strength decreased in rats on isocaloric low-protein diets compared with normal protein group (â33.4%). PTH increased pull-out strength in low-protein group, even compared to controls from the normal protein group. PTH and pamidronate increased bone volume/tissue volume, bone-to-implant contact, and trabecular thickness, whilst trabecular separation was reduced, with a shift to more plate-like bone surrounding the implants. Conclusions: PTH reversed the deleterious effects of long-term protein undernutrition on mechanical fixation and bone microarchitecture and improved implant osseointegration more than pamidronate or renutrition, likely through changes to structure model inde
Benign fibrous histiocytoma of bone in a paediatric population: a report of 6 cases
Case records and radiological investigations of six children with benign fibrous histiocytoma were studied retrospectively. BFH occurred in the femur (n=2), tibia (n=2) and fibula (n=2). Clinically, patients reported pain from the lesion lasting several months (mean 6months). The pain was not associated with pathological fracture in any patient. On X-rays, the lesions appeared as lytic and sharply demarcated with a sclerotic rim and fine trabeculations. The reported cases were located in the metaphysis and the diaphysis of the long bones. The tumour was restricted to bone, without periosteal or soft tissue reaction. Treatment consisted of careful intralesional curettage of the lesion; the defect was thereafter filled with bone bank graft or injectable phosphocalcic cement. The length of follow-up ranged from 24months to 4.75years (mean 35.2months). One case presented with recurrence of the disease and required successful repeat intralesional curettage. Benign fibrous histiocytoma is probably underestimated among patients less than 20years of age. This diagnosis should be considered in any child or teenager who presents with a non-ossifying fibroma accompanied by unexplainable pain or a rapid growing. Surgery restricted to the osteolytic lesion seems sufficient to achieve bone healin
Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway
<p>Abstract</p> <p>Background</p> <p>Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of <it>Plasmodium falciparum </it>CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2ÎČ1 and PfCK2ÎČ2.</p> <p>Results</p> <p>We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2ÎČ1 and PfCK2ÎČ2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2ÎČ1 or HA-PfCK2ÎČ2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2ÎČ1- and PfCK2ÎČ2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2ÎČ1 and PfCK2ÎČ2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2α <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.</p
The active metabolite of leflunomide, A77 1726, inhibits the production of prostaglandin E2, matrix metalloproteinase 1 and interleukin 6 in human fibroblastâlike synoviocytes
Objectives. To investigate the effects of the active metabolite of leflunomide, A77 1726, on fibroblastâlike synoviocytes. In rheumatoid arthritis (RA) synoviocytes participate in tissue destruction by producing metalloproteinases (MMP), prostaglandin E2 (PGE2) and interleukin (IL) 6, which are involved in extracellular matrix degradation, resorption of the mineral phase and osteoclastâmediated bone resorption. Methods. Human synoviocytes were stimulated with ILâ1α or tumour necrosis factor α (TNFâα) in the presence of A77 1726. Culture supernatants were analysed for production of interstitial collagenase (MMPâ1), tissueâinhibitor of metalloproteinases 1 (TIMPâ1), PGE2 and ILâ6. Total RNA was isolated and analysed for steadyâstate levels of MMPâ1, cyclooxygenaseâ2 (COXâ2) and ILâ6 mRNA. Results. A77 1726 inhibited the production of PGE2 in synoviocytes activated by TNFâα and ILâ1α with median inhibitory concentrations (IC50) of 7 and 3â”m respectively. In contrast, MMPâ1 and ILâ6 production was inhibited at high A77 1726 concentrations (> 10â”m), whereas TIMPâ1 was not affected. The inhibition of MMPâ1 and ILâ6 production was due to the known inhibitory effect of A77 1726 on pyrimidine synthesis, as it was reversed by the addition of uridine. This did not apply to PGE2 production, which was inhibited via direct action of A77 1726 on COXâ2, as shown by the increasing amount of substrate (arachidonic acid) in the culture medium. Conclusion. This study shows that some of the beneficial effect of leflunomide in RA patients may be due to the inhibition of PGE2, ILâ6 and MMPâ1 production in synoviocytes. This effect, coupled with its multiple inhibitory effects on T lymphocyte functions, might account for the significant reduction in the rate of disease progression in RA patients treated with leflunomid
[HDL inhibit cytokine production in a mouse model of urate crystal-induced inflammation].
Objectives: To evaluate whether high density lipoproteins (HDL) affect monosodium urate (MSU) crystal-induced inflammation in the murine air pouch model. Methods: MSU crystals were prepared by Denko's method and sterilized by heating at 180°C for 2 h before each experiment. Human HDL were isolated from peripheral blood of healthy volunteers. MSU crystals (2 mg in 1 ml of PBS) were injected into subcutaneous air pouches in mice in the presence or absence of HDL (0.1 mg). Negative control pouches received 1 ml of PBS. To recover pouch fluid, the pouches were washed with 2 ml of PBS after the animals were sacrificed. The leukocyte count in the lavage fluids was obtained using a hemocytometer and differential leukocyte count was determined by May-GrĂŒnwald-Giemsa staining. IL-6, KC, CCL2 and TNF-α levels were measured in exudates by ELISA. Results: MSU crystals increased the number of leukocytes and the neutrophil migration, as well as the concentrations of IL-6, KC and CCL2 in pouch fluids, while the TNF-α levels were not detectable. The treatment with HDL led to a reduction in all inflammatory parameters: the leukocyte count decreased by 73%; the neutrophil density decreased by 35%; the IL-6, KC and CCL2 concentration decreased by 4-, 6- and 5-fold respectively. Conclusions: This study shows that HDL may limit the inflammatory process by inhibiting leukocyte recruitment and cytokine release. HDL are likely to represent a mechanism of control of crystal-induced inflammation
Factors influencing digital review of pathology test results in an inpatient setting: a cross-sectional study
This is the final version. Available from Oxford University Press via the DOI in this record.Availability of data and material:
The datasets generated and/or analysed during the current study are not publicly available due to the
remote possibility of targeted patient re-identification through a linkage attack. Limited data may be
available from the corresponding author on reasonable request, and review by the information
governance and ethics teams.BACKGROUND: Delay or failure to view test results in a hospital setting can lead to delayed
diagnosis, risk of patient harm, and represents inefficiency. Factors influencing this were
investigated to identify how timeliness and completeness of test review could be improved through
an evidence based redesign of the use of clinical test review software.
METHODS: A cross section of all abnormal haematology and biochemistry results which were published on a digital test review platform over a three year period were investigated. The time it
took for clinicians to view these results, and the results that were not viewed within 30 days, were
analysed relative to time of the week, the detailed type of test, and an indicator of patient record
data quality.
RESULTS: The majority of results were viewed within 90 minutes, and 93.9% of these results
viewed on the digital platform within 30 days. There was significant variation in results review
throughout the week, shown to be due to an interplay between technical and clinical workflow
factors. Routine results were less likely to be reviewed, as were those with patient record data
quality issues .
CONCLUSION: The evidence suggests that test result review would be improved by stream-lining
access to the result platform, differentiating between urgent and routine results, improving
handover of responsibility for result review, and improving search for temporary patient records.
Altering the timing of phlebotomy rounds, and a review of the appropriateness of routine test
requests at the weekend may also improve result review rates.Engineering and Physical Sciences Research Council (EPSRC)NHS EnglandAlan Turing Institut
Diagnosis of acute toxoplasmosis in pregnant women referred to therapeutic centers of Alborz Province (Iran) using immunoglobulin G avidity ELISA technique
Objective To evaluate immunoglobulin G (IgG) avidity as a useful and reliable technique in diagnosing toxoplasmosis in pregnant women referring to therapeutic centers of Alborz Province (Iran) in 2014, against two other tests, IgG and immunoglobulin G (IgM) anti-Toxoplasma. Methods Serum samples (468 in total) were obtained from different therapeutic centers in Karaj City. ELISA method was used to test the anti-Toxoplasma avidity of IgG, IgM and IgG. The data were analyzed by descriptive statistical methods and Chi-square test (P < 0.05) using SPSS 17.0. Results Anti-Toxoplasma avidity tests of IgM and IgG were positive in 9 and 86 samples respectively. Also, a borderline IgM avidity was detected in 2 suspected samples. In addition, among all positive and suspected samples, 79 cases indicated high titers of IgG avidity, 7 cases were of low titers and 1 case was of a borderline titer. The prevalence of anti-Toxoplasma antibodies was 20. The sera which showed high avidity index was obtained from patients at chronic phase of infection (77.7) while those which showed low avidity levels were from patients at acute toxoplasmosis (92). Conclusions This study clearly showed that acute and chronic phases of toxoplasmosis could be differentiated with the aid of IgG avidity test. This test may also assist in recognizing old and newly acquired infections. Ă© 2016 Asian Pacific Tropical Medicine Pres
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