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Selected AbstractspH changes in external root surface cavities after calcium hydroxide is placed at 1, 3 and 5 mm short of the radiographic apexDENTAL TRAUMATOLOGY, Issue 5 2009Thaddeus M. Chamberlain The root canals of single-rooted anterior human teeth were cleaned and shaped after decoronation. Cavities about 0.50 mm deep and 1.0 mm wide located at 1, 3 and 5 mm from the radiographic apex were prepared on the external root surface and the teeth were randomly divided into four groups. The roots were filled with calcium hydroxide at 1, 3 and 5 mm from the radiographic apex, and the control group was left empty. pH readings were obtained at intervals over a 28-day study. The roots which were filled within 1 mm of the radiographic apex had the greatest increase in pH in each of the cavities. These results demonstrate that the greatest pH change on the external root surface near the apex is obtained when the canal is more completely filled with calcium hydroxide. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Sustained hypoxia enhances chondrocyte matrix synthesisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2009Christian H. Coyle Abstract Articular cartilage is an avascular tissue with chondrocytes in the deeper zones existing under conditions of sustained hypoxia. Using a hypoxic chamber to provide controlled hypoxia, this study was performed to determine whether sustained hypoxia enhances the production of cartilage matrix proteins. Freshly isolated primary bovine articular chondrocytes were encapsulated in three-dimensional alginate beads and maintained at 2% oxygen with media changes using media pre-equilibrated to 2% oxygen. Immunolocalization of HIF-1, was performed to verify hypoxic conditions. Sustained hypoxia resulted in an increase in proteoglycan synthesis after only 1 day, as measured by 35S-sulfate incorporation. This increase was maintained for the duration of the 17 day study. After 17 days of hypoxic culture, increases in total type II collagen and COL2A1 gene expression were probed by indirect immunofluorescence, type II collagen ELISA, and real-time qPCR; in addition, increased glycosaminoglycan deposition was observed as determined by chemical analysis. These studies show that sustained hypoxia enhances articular chondrocyte matrix synthesis and viability in three-dimensional alginate culture. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 793,799, 2009 [source] Chemical Stability of an Admixture Combining Ziconotide and Bupivacaine During Simulated Intrathecal AdministrationNEUROMODULATION, Issue 2007David Shields PhD ABSTRACT Objective., To determine the stability of an admixture combining ziconotide with bupivacaine hydrochloride during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods., An admixture containing ziconotide (25 µg/mL) and bupivacaine hydrochloride (5 mg/mL) was stored in SynchroMed® II pumps at 37° and in control vials at either 37° or 5°. Using high-performance liquid chromatography, drug concentrations were determined from samples obtained at varying intervals during the 30-day study. Results., After 30 days, pump ziconotide and bupivacaine hydrochloride concentrations measured an average of 86.9% and 99.4% of their initial concentrations, respectively. Control vials displayed similar degradation rates for both drugs. Statistical evaluation of the ziconotide 95% confidence interval indicated that the ziconotide concentration would meet or exceed 90% and 80% of initial concentration for 22 days and 45 days, respectively. Conclusions., An admixture containing 25 µg/mL ziconotide and 5 mg/mL bupivacaine hydrochloride was 90% stable for 22 days and 80% stable for 45 days (extrapolated) in SynchroMed® II infusion pumps. [source] Evaluation of the environmental fate of thymol and phenethyl propionate in the laboratoryPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2008Dingfei Hu Abstract BACKGROUND: The natural monoterpenoid pesticides thymol and phenethyl propionate (PEP) are used indoors and outdoors, but their fate in the environment has not been reported. In order better to understand their impact on the environment, water metabolism and soil metabolism studies were conducted with thymol and PEP at a concentration of 10 µg g,1 in water and in soil under laboratory conditions. RESULTS: Dissipation half-lives of thymol and PEP were 16 and 5 days in water and 5 and 4 days in soil. 2-Phenylethanol and 2-(4-hydroxyphenyl)ethanol were detected as primary degradation products of PEP. Over time, a considerable volatilization loss of thymol, but not of phenethyl propionate, was found in the 1 month study under the experimental conditions used. Less than 6% of thymol and PEP were detected as bound residues, and less than 3% were mineralized during the 30 day study. CONCLUSION: In order to maximize the pesticidal effect, more attention should be paid to the temperature for thymol than for PEP when they are being applied, owing to the high volatility of the former. Thymol and PEP pose low risks to the ecosystem because of their rapid dissipation and low bound residues in the environment. Copyright © 2008 Society of Chemical Industry [source] Monitoring pollution by proton-transfer-reaction mass spectrometry during paediatric anaesthesia with positive pressure ventilation via the laryngeal mask airway or uncuffed tracheal tubeANAESTHESIA, Issue 7 2002J. Rieder Summary Twenty children aged 2,66 months were randomly allocated for airway management with either the laryngeal mask airway or uncuffed tracheal tube using intermittent positive pressure ventilation with a tidal volume of 8 ml.kg,1 and a respiratory rate adjusted to maintain end-expiratory carbon dioxide concentration at 5.3 kPa. Induction was with fentanyl/propofol and maintenance was with sevoflurane 2.5% in oxygen/air. The airway device was removed when the patients were awake and the patients were transferred to the postanaesthesia care unit 10 min later. Air was sampled from a point 1.5 m above the floor at a location remote from the ventilation outlet and analysed using a proton-transfer-reaction mass spectrometer capable of continuous trace gas analysis at the parts per billion volume (ppbv) level. The concentration of sevoflurane was recorded every minute during three consecutive phases: for 5 min before the introduction of sevoflurane (background); after introduction of sevoflurane until removal of the airway device (intra-operative); and every minute after removal until the concentration returned to background levels. Median (interquartile range [range]) intra-operative sevoflurane concentrations were 200,400 times higher than background values for the laryngeal mask airway 1 (1,2 [0,3]) ppbv vs. 404 (278,523 [83,983]) ppbv, respectively, and the tracheal tube 2 (1,3 [0,5]) ppbv vs. 396 (204,589 [107,1735]) ppbv (both p <,0.0001), and returned to background values within 5 min of removal. There were no differences in sevoflurane concentration between devices intra-operatively or after removal. The performance of the proton-transfer-reaction mass spectrometer was identical at the start and end of the 30-day study. We conclude that peri-operative sevoflurane concentration in a modern operating theatre is similar for the laryngeal mask airway and the uncuffed tracheal tube in paediatric patients receiving intermittent positive pressure ventilation. Intra-operative sevoflurane concentrations are five times lower than occupational safety limit requirements, and 1000 times lower 5 min after removal of the airway device with the patient awake. The proton-transfer-reaction mass spectrometer has potential for monitoring air quality in the operating theatre. [source] Gentamicin-induced readthrough of stop codons in duchenne muscular dystrophyANNALS OF NEUROLOGY, Issue 6 2010Vinod Malik PhD Objective The objective of this study was to establish the feasibility of long-term gentamicin dosing to achieve stop codon readthrough and produce full-length dystrophin. Mutation suppression of stop codons, successfully achieved in the mdx mouse using gentamicin, represents an important evolving treatment strategy in Duchenne muscular dystrophy (DMD). Methods Two DMD cohorts received 14-day gentamicin (7.5mg/kg/day): Cohort 1 (n = 10) stop codon patients and Cohort 2 (n = 8) frameshift controls. Two additional stop codon DMD cohorts were gentamicin treated (7.5mg/kg) for 6 months: Cohort 3 (n = 12) dosed weekly and Cohort 4 (n = 4) dosed twice weekly. Pre- and post-treatment biopsies were assessed for dystrophin levels, as were clinical outcomes. Results In the 14-day study, serum creatine kinase (CK) dropped by 50%, which was not seen in frameshift DMD controls. After 6 months of gentamicin, dystrophin levels significantly increased (p = 0.027); the highest levels reached 13 to 15% of normal (1 in Cohort 3, and 2 in Cohort 4), accompanied by reduced serum CK favoring drug-induced readthrough of stop codons. This was supported by stabilization of strength and a slight increase in forced vital capacity. Pretreatment stable transcripts predicted an increase of dystrophin after gentamicin. Readthrough efficiency was not affected by the stop codon or its surrounding fourth nucleotide. In 1 subject, antigen-specific interferon-, enzyme-linked immunospot assay detected an immunogenic dystrophin epitope. Interpretation The results support efforts to achieve drug-induced mutation suppression of stop codons. The immunogenic epitope resulting from readthrough emphasizes the importance of monitoring T-cell immunity during clinical studies that suppress stop codons. Similar principles apply to other molecular strategies, including exon skipping and gene therapy. ANN NEUROL 2010;67:771,780 [source] Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Maria V. Papadopoulou The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source] Toxicity Profile of Lisdexamfetamine Dimesylate in Three Independent Rat Toxicology StudiesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2007Suma Krishnan The toxicity profile of orally administered LDX has been evaluated in rats. In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity. At 1000 mg/kg, one rat died and another was euthanized. In a 7-day repeat-dose study, all rats dosed with LDX (14 per dose group for each sex) showed increased activity; 10 male rats and 11 female rats at 300 mg/kg/day and 3 female rats at 100 mg/kg/day were euthanized because of self-mutilation and 1 male rat at 300 mg/kg/day was found dead. In a 28-day study, only rats at 80 mg/kg showed signs of self-mutilation and thin body condition. In both the 7- and 28-day studies, LDX caused significant changes in some blood chemistry parameters (e.g. blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase) and organ weights (e.g. particularly heart, liver, brain, and spleen). Overall, no apparent treatment-related histopathologic changes were observed. Toxicokinetic assessments indicated that as the dose of LDX was increased, rats were exposed to increasing levels of LDX and d -amphetamine. The extent of exposure to LDX and d -amphetamine increased after repeated-dose in the 28-day study. The findings of the repeat-dose studies indicate that the toxicity profile in rats administered LDX orally is comparable to that for d -amphetamine; however, the apparent lethal dose of LDX in rats is more than five times higher than the LD50 of orally administered d -amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine. [source] Die Fotografie , ein neues Bildmedium im Wissenschaftspanorama des 19.BERICHTE ZUR WISSENSCHAFTSGESCHICHTE, Issue 2 2005Jahrhunderts. Abstract Photography , a novel medium of scientific representation in the XIXth century array of arts and sciences. To delve into various nineteenth century academic disciplines under the heading ,photography in the arts and sciences' as did last year's annual conference of the History of Science Society , the interest in such a topic only partly stems from the ,iconic turn' that has generally enlarged the scope of the social sciences in recent years. A more poignant feature in any such present day study will probably be a basic scepticism facing the fact that in public use photographs have been manipulated in many respects. Yet, while shying away from any simple success story, a historically minded approach to changing ,visual paradigms' (Historische Bildwissenschaft) has begun to emerge. In this context, it has proved of considerable heuristic value to reconsider the role of early photography in an array of science, arts and technology: Since the reliance on the traditional ways of sketching reality persisted, in many an instance where photography was introduced, the thoughts the pioneer photographers had about their new, seemingly automated business, call for close attention. Thus scholarship sets up a parallel ,discussion room'; the lively debate on the benefit of academic drawings as opposed to photographic portraits is a case in point. Some fairly specialised reports on photographically based analyses, such as electron microscopy, point to a borderline where the very idea of representation as a correspondence of reality and imagination gets blurred. Even though any ,visual culture' will have to shoulder the ,burden of representation', it is equally likely that it will offer a deeper sensibility for the intricacies entailed in the variegated ways of illustrating or mapping chosen subjects of scientific interest. Scholarship may thus somewhat control the disillusionment that by now has become the epitome of writing on photographic history. Provided with a renewed methodological awareness for the perception process and its photographic transition, historians may strike a better balance between the ever present tendencies of a realistic and an aesthetic way of picturing the world we live in. [source] | |||||||||||||