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In another aspect, the invention provides a release coating composition as defined above, wherein the solution comprises from about 2% to about 40% by weight, preferably from about 2% by weight to about 15% by weight of low viscosity hydroxypropyl methylcellulose having hydroxypropyl molar substitution of from 0 to about 82 in water, wherein low viscosity means the viscosity of a 2% by weight of a solution of hydroxypropyl methylcellulose in water is up to 100 centipoise at room temperature 20.
Butterfield and J. Folkman Children's Hospital, Boston ; . These cells were maintained in culture in Dulbecco's modified Eagle's medium DMEM ; GIBCO ; with 10%6 calf serum HyClone ; [DMEM 10 supplemented with basic fibroblast growth factor bFGF ; 3 ng ml ; Heparinase Purification and Characterization. Heparinases were purified 11, 12 ; and extensively desalted using a Centricon P-30 molecular size cutoff, 30 kDa ; Amicon ; Heparinases I, II, and III were collected in a microcentrifuge tube and lyophilized VirTis Freeze mobil model 12, VirTis ; . Protein concentration was determined by use of the Micro BCA reagent Pierce ; relative to a bovine serum albumin standard. ; The purity of the peak was determined by highpressure liquid chromatography using a Vydac C18 reversephase column in a HP 1090 Hewlett-Packard ; , with diode array detection, in a gradient of 0-80%o acetonitrile in 0.1% trifluoroacetic acid for 60 min. Protein was monitored at 210 and 277 nm. Mass spectrometry was performed on the heparinase preparations; -2 , g of heparinase was mixed with 1 dul of sinapinic acid 10 mg ml ; in 80%6 acetonitrile 0.1% trifluoroacetic acid in water ; 1: vol vol ; and then analyzed by laser desorption mass spectrometry Laser MAT, Finnigan, CA ; . In Vivo Neovascularization Assay. To determine whether heparinases inhibited neovascularization in vivo, the chorioallantoic membrane CAM ; assay was performed as described 13, 24 ; . Briefly, on day 3 of the development, fertilized chicken embryos were removed from their shells and placed in plastic Petri dishes. On day 6, heparinase I 100 pmol ; was mixed in methylcellulose disks and applied to the surfaces of the growing CAMs above the dense subectodermal plexus. After a 48-hr exposure of the CAMs to heparinase I, India ink Liposyn was injected intravascularly as described. For histological analysis, tissue specimens were fixed in formalin, rinsed in 0.1 M cacodylate buffer pH 7.4 ; , and embedded in JB-4 plastic Polyscience ; at 40C. Threemicrometer sections were cut with a Reichert 2050 microtome and stained with toluidine blue; micrographs were taken on a Zeiss photomicroscope with Kodak TM x 100 ; and a green filter. Endothelial Cell Proliferation Assay. Bovine capillary endothelial cells BCEs ; [104 cells per 0.5 ml with 5% calf serum DMEM 5 ; ] were plated onto gelatin-coated 24-well tissue culture dishes and allowed to attach overnight. On day 2, unattached cells were removed and the attached cells were fed DMEM 5 again. Heparinases and bFGF 12 ng ml; Takeda, Osaka ; were added. Wells containing phosphatebuffered saline PBS ; alone and PBS and bFGF were included as controls. On day 5, medium was aspirated and cells.
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How you can help ACT UP continue to act up In the last several years, ACT UP Philadelphia has been the most powerful of the few surviving chapters around the country. With the New York City chapter, Philly gained price reductions on a new HIV drug and organized the march for drug treatment access in South Africa during the international AIDS conference last July. They followed the presidential candidate Al Gore around the country, demanding that the U.S. allow third world countries to manufacture generic versions of HIV drugs. All of this depletes the money they manage to scavenge together, not to mention their round-the-clock time. Now, they're being dealt heavy blows by the powers that be. Instead of casual arrests during last summer's Republican Party Convention protests in Philadelphia, ACT UP Philly members along with other activists were kicked, beaten, hog-tied and had their heads slammed into a wall by police officers. They were levied extremely high bonds, including one for one million dollars. Please help the legal defense by sending contributions. The City of Philadelphia is refusing all plea bargaining. Show the authorities that freedom fighters will never be forsaken. Send donations and make checks out to: ACT UP Philadelphia, P.O. Box 22439, Land Title Station, Philadelphia, PA 19110-2439. 18 Positively Aware January February 2001.
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Approximately 240, 480 total cases of breast cancer will be diagnosed this year, including more than 178, 480 cases of invasive breast cancer and 62, 000 cases of in situ breast cancer. 40, 460 women and 450 men in the U.S. will die from the disease annually. At this time, there are over 2 million breast cancer survivors in the U.S. who have been treated for breast cancer. One person is diagnosed approximately every 3 minutes, and one person dies of breast cancer approximately every 14 minutes. The chance of a woman having invasive breast cancer some time during her life is about 1 in 8. People over the age of 50 account for 76% of breast cancer cases. Breast cancer is the most commonly diagnosed cancer among Hispanic women and is the leading cause of cancer deaths among this group. White, non-Hispanic women are more likely to develop breast cancer but African-American women are more likely to die from it and methyldopa.
Table 3. Means "SD ; and P values of clinical, biochemical, histomorphometric and histodynamic parameters in the histological classes HP Number MuF Age years ; HD time months ; PTH intact pguml ; PTH 1-84 pguml ; PTH Total pguml ; BGP nguml ; BALP Uul ; AP Uul ; 25-OHD3 nguml ; 1-25 OH ; 2D3 pguml ; Ca mgudl ; P mgudl ; BV-TV % ; OV-BV % ; O.Th mm ; ObS-BS % ; ES-BS % ; OcS-BS % ; MAR mmuday ; BFRuBS mm3umm2uday ; Aj.AR mmuday ; Mlt days ; OPG pguml ; 12 6u6 57.17"10.62 MO 17 13u4 56.82"12.49 ABD 7 7u0 60.14"12.77 ANOVA.
Or larger, 21 18% ; were diameter, and 79 69% ; were less than 5 mm in diameter. Of 70 studies, 54 77% ; revealed findings positive for adenornas. The sensitivity and specificity of CT colography in diagnosis of adenoma and patient identification are summarized in Table 1. The sensitivity of identification of patients with adenomas 10 mm in diameter or larger was 75% nine of 12 ; , with a specificity of 91% for both observers. For patients with adenornas 5 mm in diameter or greater, the sensitivity and specificity averaged 66% and 63%, respectively. Patients with adenomas smaller than 5 mm in diameter were identified less than 45% of the time, with an average specificity of 80%. With CT colography, 11 73% ; of 15 adenomas 10 mm and methysergide.
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Overall, the observed toxicity symptoms were typical for glucocorticoid toxicity. Signs of toxicity were observed at lower doses for the subcutaneous and peritoneal route compared to the oral route. No systemic signs of toxicity were recorded following dermal administration of 4000 mg kg hydrocortisone aceponate. The hydrocortisone aceponate product was not considered harmful via oral, dermal or inhalation administration, nor was it a dermal irritant and does not appear to be a sensitising agent Buehler test ; . It was, however, an ocular irritant and warnings to this effect are included in the SPC. Repeated dose toxicity The changes observed during 8 repeated dose toxicity studies in different species were related to its glucocorticoid activity. The principal organs of toxicity were stomach, lungs, spleen, thymus, adrenals, pituitary, kidney and liver. Subconjunctival administration was the most sensitive route tested in repeated dose toxicity studies with a NOEL of 0.127 mg hydrocortisone aceponate per day in hydrophilic cream ; being identified in rabbits and rats. Subcutaneous and cutaneous administration resulted in similar NOELs 0.33 mg and 0.3175 mg hydrocortisone aceponate per kg bodyweight per day, respectively, in rabbits ; . At doses above the NOEL, chronic toxicity was weaker by the cutaneous route compared to the subcutaneous route, indicated by a marked reduction in the magnitude of findings for cutaneous compared to subcutaneous administration. No difference in NOEL was recorded for abraded or intact skin. Aqueous hydroxypropyl methylcellulose gel, cream or ointment vehicles were used in the repeated dose toxicity studies. Reproductive toxicity, including teratogenicity According to Annex I of Directive 2001 82 EC as amended by 2004 28 EC, it is not required to conduct studies on the effects on reproductive toxicity when the systemic absorption of a topical treatment is negligible. This criteria was fulfilled since the bioavailability of hydrocortisone aceponate in the target species was estimated to be 0.2% after 7 days of cutaneous application of the hydrocortisone aceponate product at the intended therapeutic dose. A series of 4 older studies examining the reproductive toxicity of hydrocortisone aceponate was provided. Embryotoxic and teratogenic effects of hydrocortisone aceponate, including skeletal changes, reduction in foetal and placental weight and elevated post-implantation losses, were seen in rats and rabbits at higher doses. No effects were seen on the length of gestation in either species. A reduction in the survival of the resulting offspring was also observed. The lowest NOELs for reproductive toxicity were in the rabbit during the organogenesis period where embryotoxic effects were seen at 0.33 mg kg NOEL 0.1 mg kg ; . No studies of reproductive toxicity in the target species were provided. As a consequence of this the applicant has included a warning regarding the use of Cortavance in pregnant animals in the SPC.
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A methylcellulose serial replating assay6 was used to assess the effects of MLL-AF10 on the in vitro growth properties of murine myeloid progenitors Figure 1 ; . The MSCV was employed to transduce freshly harvested BM cells from mice treated 5 days previously with 5-flurouracil. MSCV constructs encoded either MLL-AF10, MLL sequences 5 of the translocation breakpoint MLL5 ; , or AF10 amino acids 682 to 1085 with an amino-terminal FLAG tag FLAG-AF10 ; . Retroviral transduction efficiency, determined for each construct by plating transduced BM cells under selective G418 ; and nonselective conditions, ranged from 40% to 60% in various experiments not shown ; . Western blotting of extracts from transiently transfected retroviral packaging cells confirmed that the MLL5 and FLAG-AF10 constructs were efficiently expressed not shown ; . Plating of cells transduced with the 3 MSCV constructs under selective conditions showed similar numbers, size, and morphology of myeloid colonies after 7 days in primary methylcellulose cultures Figure 1B and data not shown ; . However, significant differences were observed in a second round of plating initiated by 104 cells pooled from colonies harvested from first-round cultures. MLL-AF10transduced cells gave rise to hundreds of colonies in second- and third- ; round platings, while cells from MLL5 - or FLAG-AF10transduced cultures produced few or no secondary colonies Figure 1B ; . In addition, single-cell suspensions from second- and third-round cultures were readily and metolazone.
Necas, J.1, Bartosikova, L.1, Suchy, V.1, Kubinova, R.1, Liskova, M.1, Bartosik, T.2, Janostikova, E.1, Florian, T.1, Frydrych, M.1, Krcmar, J.1, Klusakova, J.2, Parak, T.1, Gpfert E.3 1 Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno; 2 St. Annes University Hospital in Brno; 3 Veterinary Research Institute Brno The goal of the study was to monitor the antioxidative effect of pomiferine in the conditions of ischemia-reperfusion of laboratory rat kidney tissue. 40 animals were subject to kidney tissue ischemia 60 minutes ; followed by reperfusion 10 minutes ; . After that, the animals were divided by random selection into 4 groups n 10 ; . The treated groups were given pomiferine in peroral doses of 5, 10 and 20 mg kg in 0.5% solution of methylcellulose E5 once a day, the placebo group was given only the solution of Methocel E5. One group n 10 ; was an intact group without ischemia-reperfusion and without treatment ; , for comparison. Once a week, selected laboratory parameters were determined in all animals. On the 15th day the animals were exsanquined and organs were recovered for histopathological examination. We discovered a statistically significant changes of the superoxiddismutase and glutathione peroxidase catalytic activity; changes of total antioxidative capacity and malondialdehyde in the treated groups compared to the groups of placebo and intact. Other examined laboratory parameters creatinine, urea and uric acid in blood; creatinine, urea, total protein in urine; diuresis ; exhibit the significant changes too. The results of biochemical examination show a protective antioxidative effect of pomiferine. The results of histopathological examination support this assumption. This work was supported by project IGA MZ No. NL 7455-3 Key words: pomiferine, antioxidantive enzymes, total antioxidative capacity, malondialdehyde, ischemia-reperfusion of kidney.
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| Methylcellulose breastfeedingINDICATIONS AND CLINICAL USE DITROPAN XL oxybutynin chloride ; is indicated for the relief of the symptoms of urge incontinence, urgency and frequency in patients with overactive bladder U-UI ; . Geriatrics 65 years of age ; : The safety and efficacy of DITROPAN XL are similar in patients younger or older than 65 years. Pediatrics 18 years of age ; : The safety and efficacy of DITROPAN XL in children have not been established and micafungin.
Human CB cells were thawed, and CD34 + cells were enriched using a negative StemSep column system StemCell Technologies Inc, Vancouver, British Columbia, Canada, : stemcell ; according to the supplier's directions. For gene expression analysis and methylcellulose assays, human CB cells.
Summary A high proportion of the CD34 + CD38 - cells in normal human marrow are defined as longterm culture-initiating cells LTC-IC ; because they can proliferate and differentiate when cocultured with cytokine-producing stromal feeder layers. In contrast, very few CD34 + CD38 cells will divide in cytokine-containing methylcellulose and thus are not classifiable as direct colony-forming cells CFC ; , although most can proliferate in serum-free liquid cultures containing certain soluble cytokines. Analysis of the effects of 16 cytokines on CD34 + CD38 - cells in the latter type of culture showed that Flt3-1igand FL ; , Steel factor SF ; , and interleukin IL ; -3 were both necessary and sufficient to obtain an N30-fold amplification of the input L T C - population within 10 d. As single factors, only FL and thrombopoietin TPO ; stimulated a net increase in L T within 10 d. Interestingly, a significantly increased proportion of the CFC produced from the TPO-amplified L T C - I were erythroid. Increases in the number of directly detectable CFC of 500-fold were also obtainable within 10 d in serum-free cultures of CD34 + CD38 - cells. However, this required the presence o f l and or granulocyte colonystimulating factor and or nerve growth factor 13 in addition to FL, SF, and IL-3. Also, for this response, the most potent single-acting factor tested was IL-3, not FL. Identification of cytokine combinations that differentially stimulate primitive human hematopoietic cell self-renewal and lineage determination should facihtate analysis of the intracellular pathways that regulate these decisions as well as the development of improved ex vivo expansion and gene transfer protocols and midodrine.
| TO THE EDITOR: We read with interest the study by Dr. Volavka and colleagues comparing three second-generation antipsychotics and haloperidol in patients with chronic schizophrenia. In this study, olanzapine was randomly assigned to a second cohort of patients after the study had been in progress for 15 months. The result of the combined cohorts was that olanzapine had the largest effect size for total scores on the Positive and Negative Syndrome Scale. The authors found no cohort effect. For their statistical analysis, they assumed that if a cohort effect were present, the three first-cohort medications i.e., haloperidol, risperidone, and clozapine ; should have all fared better in the second cohort. We question this assumption. If the second cohort consisted of patients with a better prognosis for second-generation antipsychotics, we would have expected the following: haloperidol should not have been effective in either cohort because both cohorts were selected to be resistant to neuroleptics, clozapine should have performed well in both cohorts, and risperidone should have been inferior to clozapine in the first cohort 1 ; and comparable in the second cohort 2, 3 ; . The reported results fit these assumptions fairly well. Haloperidol was indeed ineffective in both cohorts. Clozapine did moderately well in both cohorts, with scores on the Positive and Negative Syndrome Scale increasing only a small amount in the second cohort 6.48 versus 7.05, respectively ; . The risperidone group's improvement scores increased from 0.03 in the first cohort N 25 ; to 7.93 in the second cohort N 16 ; . The latter appears comparable to the improvement with olanzapine 9.1, N 39 ; . In summary, the cohort results appear too different to be validly combined. Other analyses in this article seem to favor olanzapine. The authors reported that two patients had seizures while taking risperidone, but none had seizures while taking olanzapine. However, the authors did not note the discordance of the results for their small group of patients with seizure rates in the premarketing trials of these antipsychotics. According to the package inserts, there was a higher rate of seizures with olanzapine than with risperidone 0.9% and 0.3%, respectively ; . Two patients developed neutropenia with risperidone, and the authors cited a published report of another instance. They did not mention that olanzapine is associated with at least 10 cases, which we found in a PUBMED search.
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RA- 02. IMAGING AND EVALUATION OF 124 I-NM404, A TUMOR-SPECIFIC PHOSPHOLIPID ETHER, IN AN INTRACRANIAL RAT GLIOMA MODEL Raj S. Ambay, Marjorie A. Curet, Giganthy Ton, Ben A. Durkee, Marc A. Longino, Jyoti J. Watters, Garet P. Lahvis, and Jamey P. Weichert; University of Wisconsin, Madison, WI, USA Gliomas are uniformly lethal, with average survival following diagnosis of 1218 months. Biological markers that selectively visualize intracranial gliomas will be important in their diagnosis and treatment. NM404, a novel phospholipid ether analog currently in phase 1 clinical trials for human lung cancer, demonstrated striking tumor avidity in 32 of tumor models in rodents. The primary aim of this study was to examine the multimodal imaging characteristics of intracranial rat gliomas using 124I-NM404 with microPET, microCT, and contrast-enhanced microMRI. The secondary aims were to evaluate tumor brain ratios nCi cc tissue ; and histology. The goal is to provide a basis upon which NM404 can be extended to patients with gliomas. Five Fischer rats 125150 g ; were inoculated with RG2 rat glioma cells 1.5 10 6 cells 5 ml methylcellulose ; , stereotactically guided into the frontal lobe. On day 7 after inoculation, 124I-NM404 was injected 80100 mCi 0.2 ml ; by tail vein into rats bearing tumors 512 mm in diameter. By day 12, five rats displayed signs of neurological deterioration. Animals were scanned using PET, MRI with gadolinium, and CT. Brains were harvested for histological analysis, with a section of tumor sent to another laboratory for microglial studies. 124I-NM404 with PET provided an accurate image of the tumor when compared with the current gold standard of MRI with gadolinium. Fused CT and PET images provided an accurate three-dimensional anatomical model. NM404 uptake corresponded to tumor location by histology. Tumor brain ratio averaged 9.2. A declining number of viable tumor cells and an exponential growth of microglial cells were anecdotally observed over 4 days. Preliminary results suggest that NM404 displays avidity to gliomas and possible utility in the treatment of gliomas. Further studies using 125I and 124I with NM404 need to be completed in order to fully characterize the imaging and therapeutic potential prior to extension to human glioma patients and mifeprex.
Striatal tissue levels of DA was coincident with the loss of striatal DAT binding sites and thus seems to represent the magnitude of dopaminergic terminal damage in the striatum. DAT binding sites in the SNpc was also measured after METH dosing. Four doses of METH treatments dose dependently decreased DAT binding sites, and the degree of depletion was significant at higher doses Table 2 ; . These findings indicate that the dosing of METH 2 15 mg kg, 2 h apart ; produces moderate but significant dopaminergic neuronal damage and thus represents a suitable dosing paradigm to evaluate the potential of several compounds, including PARP inhibitors. In our preliminary studies, depletion of DA content in the striatum on day 4 after METH intoxication was comparable with that on day 14. Thus, the magnitude of dopaminergic terminals damage produced by METH could be stable even after 4 days. Therefore, the dosing paradigm and and methylcellulose.
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Absence of fat redistribution lipodystrophy ; . As a result, HIV + groups consisted of subjects with normal fat distribution, peripheral lipoatrophy only, visceral fat accumulation only, and a mixed phenotype peripheral lipoatrophy with visceral accumulation ; . This heterogeneity may have affected our ability to detect group differences in lipid kinetics. Future studies elucidating the contributions of SAT and VAT to lipolytic rate and FFA oxidation and whether there is site specific or overall insensitivity to exercise-induced catecholamines may provide insight into the mechanisms of fat redistribution in HIV + subjects taking HAART. The degree to which exercise stimulated palmitate oxidation was reduced in subjects with HIV was tightly related to exercise-stimulated lipolytic rate. This suggests that the reduced rate of lipid oxidation in skeletal muscle in HIV was largely due to a failure to mobilize FFA from adipose tissue stores rather than a primary defect in cellular FFA transport or mitochondrial FA utilization. Several other groups have found reduced and mifepristone.
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Bone marrow mononuclear cells 2 x lo5 cells ; from pre- and post-treatment samples were cultured in quadruplicate in alpha medium 1 mL ; containing 0.8% methylcellulose and 2-mercaptoethanol 2 x mol L ; as described., ' Erythropoietin 1 U mL ; Connaught Laboratories, Swiftwater, PA ; and giant cell tumor conditioned medium GCT-CM ; or recombinant granulocytemonocyte colony-stimulating factor GM-CSF ; and interleukin-3 IL-3 ; generously provided by Dr Steven Gillis of Immunex Corporation, Seattle, WA ; were added as sources of growth factors. BFU-E, CFU-GM, and mixed lineage colonies CFU-MIX ; of greater than 40 cells aggregate were scored using an inverted microscope after 14 days in a 37OC, 5% CO, atmosphere. Representative colonies were plucked from methylcellulose using a Pasteur pipet and Wright's-Giemsa-stained cytocentrifuge preparations were made to confirm cell lineage and miglitol.
Michigan Tech University Contact e-mail: ykyap mtu Boron nitride nanotubes BNNTs ; are recognized as the candidate that will complement the uses of carbon nanotubes CNTs ; in nanoscale science and engineering. However, high growth temperatures 1100 o C ; , low production yield, and impurities have prevented effective synthesis and applications of boron nitride nanotubes BNNTs ; in the past ten years. For the first time, we have succeeded on the growth of pure BNNTs on substrates at 600 o C [1]. This was realized based on our phase selective growth model, where energetic growth species play an important role on controlling the phases of BN solids. We verified that BNNTs can be grown in a total resputtering region, where other BN phases were suppressed. Bundles of BNNTs can be grown vertically aligned in regular patterns. These BNNTs can be used for applications without purification. Tunneling spectroscopy indicates that the BNNTs are having energy band gaps of 4.4-4.9 eV. Results generated by plasma-enhance pulsed-laser deposition PE-PLD ; and chemical vapor deposition PE-CVD ; will be discussed in the conference. YKY acknowledge supports from NSF CAREER award, the Dept. of the Army, Michigan Tech Research Excellence Fund, and CNMS at ORNL. [1]. Wang et al., Nano Letters.5, 2528 2005 and methyldopa.
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