Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Usfda”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2005

Estimation of carboxylic acid metabolite of clopidogrel in Wistar rat plasma by HPLC and its application to a pharmacokinetic study.

A new HPLC method was developed for the estimation of carboxylic acid metabolite of clopidogrel bisulfate in rat plasma using atorvastatin as internal standard. Plasma samples were extracted with a mixture of ethyl acetate and di-chloro methane (80:20, v/v) followed by subsequent reconstitution in a mixture of water:methanol:acetonitrile (40:40:20, v/v). The chromatographic separation was achieved with gradient elution on Kromasil ODS, 250 mm x 4.6 mm i.d., 5 microm analytical column maintained at 30 degrees C. Carboxylic acid metabolite of clopidogrel as well as the internal standard were detected at a wavelength of 220 nm. The method was validated as per USFDA guidelines. Calibration curves were linear in the concentration range of 125.0-32,000 ng/ml and the correlation coefficient was better than 0.999. The extraction efficiency for the carboxylic acid metabolite of clopidogrel was more than 85.76%. The intra-day accuracy ranged from 98.9% to 101.5% with a precision of 1.30% to 6.06%. Similarly, the inter-day accuracy was between 96.2% and 101.1% with a precision of 3.47% to 4.30%. The drug containing plasma samples were stable at -70 degrees C for 48 days and at ambient temperature for 24h. In the auto-sampler maintained at 15 degrees C, the processed and reconstituted samples were stable for 35 h. The drug containing frozen plasma samples were stable enough to with stand three freeze thaw cycles. The method was successfully applied to the pharmacokinetic study of the two different polymorphs of clopidogrel bisulfate in Wistar rat.

Animals↗
PubMed2003

Arrhythmia database for algorithm testing: surface leads plus intracardiac leads for validation.

Ann Arbor Electrogram Libraries (AAEL) is a database of over 500 electrocardiographic recordings made during clinical electrophysiology studies over a period of 15 years. These data are used by university researchers and cardiac device research and development laboratories to develop and test arrhythmia detection algorithms. The AAEL library is in use by all major implantable cardioverter defibrillator manufacturers as well as several Automated External Defibrillator developers. In 1996, the USFDA Center for Devices and Radiological Health licensed a portion of Volumes I for proposed device testing. The data consist of 7 channels of signals: surface leads I, III, V1, an intra-atrial high right atrium (bipolar), an intra-atrial high right atrium (unipolar), an intraventricular right ventricular apex (bipolar), and intraventricular right ventricular apex (unipolar) from the distal catheter electrode. Data were recorded under careful engineering quality control continuously (30 min-1.5 hr) on FM magnetic tape at a tape speed of 3.75 in/s after signal amplification at a filter setting of 1-500 Hz. Amplifier gain and filter settings were held constant during the entire recording procedure and a 1 mV calibration signal was entered as a reference at the time of recording. All patient recordings contain a baseline sinus rhythm, and subsequently induced ventricular tachycardia and/or ventricular fibrillation, or less frequently, supraventricular tachycardia, atrial tachycardia, and/or atrial fibrillation. Data are typically made available in digitized format (1,000 Hz); digital or FM recordings are also available. AAEL recordings are the only widespread intracardiac test files in the industry.

Arrhythmias, Cardiac↗
PubMed2006

Panax notoginseng attenuates LPS-induced pro-inflammatory mediators in RAW264.7 cells.

Herbals or dietary supplements are not regulated as drugs by the United States Food and Drug Administration (USFDA) although many may have associated therapeutic effects and toxicities. Therefore, the immunomodulatory effects of the herbal extract Panax notoginseng on cultured macrophages (RAW264.7 cells) were investigated to address potential therapeutic or toxic effects. Cells were stimulated with LPS (1 microg/ml) and treated with notoginseng at 5, 25 and 50 microg/ml. Notoginseng inhibited the LPS-induced production of TNF-alpha and IL-6 by the cultured macrophages in a concentration-dependent manner. The expression of COX-2 and IL-1 beta mRNA was also attenuated by notoginseng. TNF-alpha production was inhibited in samples treated with notoginseng 24h before, or at the same time as LPS stimulation, but not in samples treated 8h after LPS stimulation. Notoginseng reduced expression of the accessory molecules CD40 and CD86 on the RAW264.7 cells while CD14 and TLR4 expression remained unaffected. Furthermore, Rb1 and Rg1 ginsenosides also inhibited macrophage production of TNF-alpha, but to a lesser extent than did the whole notoginseng extract. Collectively, these results indicate that notoginseng inhibits LPS-induced activation of RAW264.7 macrophages and demonstrates that notoginseng possesses anti-inflammatory and immunosuppressive properties in vitro.

Animals↗
PubMed2006

Comparison of enzyme-linked immunomagnetic chemiluminescence with U.S. Food and Drug Administration's Bacteriological Analytical Manual method for the detection of Escherichia coli O157:H7.

Escherichia coli O157:H7, a major foodborne pathogen, has been associated with numerous cases of foodborne illnesses. Rapid methods have been developed for the screening of this pathogen in foods in order to circumvent timely plate culture techniques. Unfortunately, many rapid methods are presumptive and do not claim to confirm the presence of E. coli O157:H7. The previously developed method, enzyme-linked immunomagnetic chemiluminescence (ELIMCL), has been improved upon to allow for fewer incidences of false positives when used to detect E. coli O157:H7 in the presence of mixed cultures. The key feature of this assay is that it combines the highly selective synergism of both anti-O157 and anti-H7 antibodies in the sandwich immunoassay format. This work presents application of a newly semi-automated version of ELIMCL to the detection of E. coli O157:H7 in pristine buffered saline yielding detection limits of approximately 1 x 10(5) to 1 x 10(6) of live cells/mL. ELIMCL was further demonstrated to detect E. coli O157:H7 inoculated into artificially contaminated ground beef at ca. 400 CFU/g after a 5 h enrichment and about 1.5 h assay time for a total detection time of about 6.5 h. Finally, ELIMCL was compared with USFDA's Bacteriological Analytical Manual method for E. coli O157:H7 in a double-blind study. Using McNemar's treatment, the two methods were determined to be statistically similar for the detection of E. coli O157:H7 in ground beef inoculated with mixed cultures of select bacteria.

Bacteriological Techniques↗
PubMed2003

Comparison of mercury and methylmercury in northern pike and Arctic grayling from western Alaska rivers.

In western Alaska, mercury (Hg) could be a potential health risk to people whose diet is primarily fish-based. In 2000, total Hg (THg) and methylmercury (MeHg) were examined in northern pike (Esox lucius) and Arctic grayling (Thymallus arcticus) from two watersheds in western Alaska, the Yukon and Kuskokwim rivers. Whitefish (Coregonus sp.) were also examined from the Kuskokwim River. Pike from the Yukon and Kuskokwim rivers had mean concentrations of THg in muscle of 1.506 and 0.628 mg/kg wet wt, respectively. The mean concentrations of THg in grayling muscle from these rivers were 0.264 and 0.078 mg/kg, respectfully. Whitefish had a mean THg concentration in muscle of 0.032 mg/kg. MeHg, in pike and grayling constituted nearly 100% of the THg concentrations; the proportion was less in whitefish. A significant positive correlation between Hg levels and fish length was also found. Generally, there were no changes in Hg concentrations in pike or grayling over the last several years. Only pike from theYukon River had THg concentrations that exceeded the USFDA action level for human consumption of edible fish (1 mg/kg). Human hazard index for pike was > or = 1 for both adults and children, indicating a potential for toxic concern, especially among children. Further studies are needed to determine the environmental and human health impacts associated with these Hg concentrations in western Alaska, especially in the context of potentially increased consumption of resident fishes when anadromous salmon catches are reduced.

Animals↗
PubMed2002

Spontaneous homogeneous nucleation, inertial cavitation and the safety of diagnostic ultrasound.

Gas bubbles of sufficient size to serve as cavitation nuclei may form spontaneously in tissue in regions of very low interfacial tension. In the absence of an acoustic wave or other mechanical stress, such nuclei will quickly dissolve and disappear from the medium. Under the influence of an acoustic wave, however, these microbubbles may grow to many times their initial size and then collapse violently, a process known as inertial cavitation. In this work, the in vivo energetics and dynamics of the nucleation-cavitation process were modeled by treating tissue as a homogeneous fluid. The assumption of a viscosity of 10(-3) Pa s (i.e., that of water) resulted in the lowest acoustic rarefactional pressure threshold for nucleation-cavitation events, approximately 4.0 MPa, which was essentially frequency-independent over the range 1 to 15 MHz. The rarefactional pressure threshold for a viscosity of 5 x 10(-3) Pa s (that of blood) also was approximately 4.0 MPa at 1 MHz, but the threshold for this higher viscosity increased nearly linearly with frequency above approximately 5 MHz, never being more than approximately 0.2 MPa below the equivalent derated peak rarefactional pressure calculated assuming MI = 1.9, the current USFDA guideline.

Biomechanical Phenomena↗
PubMed2003

The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation.

The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1-34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1-34)NH(2) and [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH-(1-31)NH(2) to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs' ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.

Animals↗
PubMed2003

Collaborative study for the establishment of a European Phamacopoeia Biological reference preparation for Bordetella pertussis mouse antiserum for serological potency testing of acellular pertussis vaccines.

A collaborative study was organised by the European Directorate For the Quality of Medicines (EDQM) to assess the suitability of a candidate mouse antiserum as a European Pharmacopoeia Biological reference preparation (BRP) for acellular pertussis vaccine potency testing. The candidate antiserum was obtained by immunising mice with a five-component acellular pertussis vaccine: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and Fimbrial 2/Fimbrial 3 (Fim 2&3). The study has been divided into two separate phases. Phase I was a pre-qualification study including three laboratories. This phase was aimed at pre-qualifying the candidate BRP (cBRP) and at documenting the impact of differences in the antibody detection methodology enzyme linked immunosorbent assay (ELISA) procedures on results of pertussis antisera calibration versus the currently used standard US standard pertussis antiserum (mouse) Lot 1 (SPAM-1) (United States Food and Drug Administration (USFDA) reference serum) and the cBRP. As no significant difference between the antibody titres determined by using the different ELISA methodologies was found, a large-scale study enrolling 13 laboratories (Phase II) was carried out, each participant performing its in-house methodology. Its aim was to calibrate the cBRP (in terms of the SPAM-1 reference) and to demonstrate its equivalence or superiority to internal references. The study showed that there was no difference in positive sera titres expressed relative to their corresponding internal reference (homologous situation) or the proposed standard (heterologous situation) reference. The cBRP can, therefore, reliably act as replacement for the in-house reference preparations. Further analysis of the outcome of this study enabled to assign to the cBRP a potency of 39, 138, 34 and 56 ELISA unit per millilitre, respectively, to its anti-PT, anti-FHA, anti-PRN and anti-Fim 2&3 antibody contents. The cBRP has been adopted by the European Pharmacopoeia Commission at its June 2000 session as Bordetella pertussis mouse anti-serum Ph Eur. BRP batch 1.

Animals↗
PubMed2001

In vivo formation of Maillard reaction free radicals in mouse skin.

The Maillard browning reaction between carbohydrates and amines is part of an extensive series of reactions that is the basis for the brown color caused by the "sunless tanning" agent dihydroxyacetone in self-tanning products. The initial stages of the reaction are quite complex, but the ultimate products are brown polymers known collectively as melanoidins. We have now used electron spin resonance to show that radicals are produced in vivo by the Maillard reaction, initiated by treating the skin of hairless mice with a solution of dihydroxyacetone in buffer. Dihydroxyacetone was used as the carbohydrate because it is simple but highly reactive and is the only USFDA approved color additive for the production of a sunless tanning response on skin. Treated skin turned brown within 24 h and showed an electron spin resonance signal after sacrifice of the animal. The control sample, consisting of untreated skin from the same animal, remained its original pink color and had no electron spin resonance signal. In corresponding ex vivo experiments in which mouse skin was soaked in dihydroxyacetone solutions, it was conclusively demonstrated that the presence of the dihydroxyacetone was required for radical formation in skin. In both the in vivo and ex vivo reactions the electron spin resonance signal consists of a broad single line with a peak-to-peak linewidth of 15 Gauss and a g value of 2.0035. We suggest that dihydroxyacetone interacts on skin through a free radical mediated reaction similar to its in vitro reactions with amines and amino acids.

Animals↗
PubMedDate not supplied

Good laboratory practice considerations in the use of fish models.

In the late 1970's, Good Laboratory Practice Regulations (GLP) were instituted by agencies such as the USFDA, the USEPA, and the OECD to provide a system for the monitoring of animal studies submitted in support of the safety of regulated products. Although GLP regulations are regularly employed in laboratory mammal projects, they have been comparatively under-utilized in aquatic animal research. This situation is changing due to the continuing emergence of fish as toxicological and pharmaceutical test subjects, human and animal disease models, genetically-engineered food sources, and environmental sentinels. The application of GLP principles to aquatic animal studies poses a variety of challenges, especially in the areas of Study Protocol design and the creation of Standard Operating Procedures (SOP's). This presentation will highlight differences between mammalian and fish studies in the application of GLP principles, and identify specific concerns associated with the formulation of SOP's for fish projects.

Animals↗
PubMed2000

Current risk assessment approaches in different countries.

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) exist as complex mixtures in environmental and biological samples. There is sufficient evidence that the toxic congeners share a common mode of action, involving binding to the Ah-receptor. Toxic equivalency factors (TEFs) and chemical residue data are used to calculate toxic equivalent (TEQ) concentrations in environmental samples, foods, animal and human tissues. Two different approaches have been used in the risk assessments of PCDDs, PCDFs and dioxin-like PCBs. WHO and most countries outside the USA have derived Tolerable Daily (or weekly) Intakes (TDI) in the order of 1-10 pg per kg of body weight for TCDD or TEQs based on data from rodent carcinogenicity studies. These countries have assumed the existence of a threshold dose for the carcinogenicity of dioxins, while US EPA and USFDA have used probabilistic estimates of cancer potency, treating cancer as a non-threshold effect and using a descriptor that addresses upper bound risk, the Risk Specific Dose (RsD). In the USA and other countries there is a growing concern over the non-cancer effects of dioxin-like compounds. In general, the various risk assessments have identified groups of the population that are at particular high risks and all have stressed the urgent need to reduce the sources of the environmental contamination with these compounds to the lowest possible.

Benzofurans↗
PubMedDate not supplied

Polychlorinated biphenyl residues in various fatty foods consumed in Guipúzcoa, the Basque Country (Spain).

Three congeners of polychlorinated biphenyls (PCBs)--the 2, 2', 3, 4, 4', 5'-, 2, 2', 4, 4', 5, 5'-hexachloro, and 2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyls--were determined in 18 samples of butter, 44 of fish (hake and anchovy) and 24 of egg, all of which came from markets in Guipúzcoa. The total content as Araclor 1260 was also determined. Quantitation was carried out by gas chromatography in a capillary column and electron capture detector. The total content in butter ranged from 20 to 60 ng/g (fat basis), in fish from 10 to 250 ng/g (edible part), and in eggs from 1 to 10 ng/g (edible part). None of these exceeded the tolerance limits established by the Canadian Government Guideline and USFDA.

Animals↗
PubMed2004

Adalimumab: efficacy and safety in psoriasis and rheumatoid arthritis.

The next generation of targeted biologic therapies for psoriasis will either be directed against new protein targets or improve on the efficacy, safety, or convenience of medications available for an already validated area in the immune response. Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor-alpha, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. This medication is approved by the US Food and Drug Administration (USFDA) for the treatment of rheumatoid arthritis. Early phrase II studies with adalimumab have shown excellent efficacy for psoriasis with either weekly or every other week subcutaneous injection. Moreover, the safety and tolerability of adalimumab in large clinical studies of rheumatoid arthritis have shown good results. Thus, adalimumab shows significant promise for the therapy of psoriasis in the future.

Adalimumab↗
PubMed2006

MannDB - a microbial database of automated protein sequence analyses and evidence integration for protein characterization.

BACKGROUND: MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data. DESCRIPTION: MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins) are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO. CONCLUSION: MannDB comprises a large number of genomes and comprehensive protein sequence analyses representing organisms listed as high-priority agents on the websites of several governmental organizations concerned with bio-terrorism. MannDB provides the user with a BLAST interface for comparison of native and non-native sequences and a query tool for conveniently selecting proteins of interest. In addition, the user has access to a web-based browser that compiles comprehensive and extensive reports. Access to MannDB is freely available at http://manndb.llnl.gov/.

Algorithms↗
PubMedDate not supplied

Calcitonin in the prevention and therapy of osteoporotic syndromes.

It is now generally accepted that estrogen status, exercise and adequate calcium intake are the singularly most important factors which guarantee the assumption of genetically programmed peak bone mass. Physicians also recognize that estrogen replacement therapy is not only essential to prevent bone loss in the early postmenopausal female, but also for the long-term preservation of bone mineral density. The efficacy of either continuous or intermittent calmon calcitonin administration in preventing further bone loss and in some instances decreasing fracture incidences in established osteoporotic syndromes is currently well established. As noted during a variety of controlled investigations performed both in the United States and abroad, and in the Physician's Resource Manual on Osteoporosis published by the United States National Osteoporosis Foundation, salmon calcitonin is also effective in early postmenopausal women who are not candidates for estrogen replacement therapy in addition to those patients with established osteoporosis. The practicing physician should acknowledge that of all the anti-resorptive agents recommended for therapy in osteoporotic syndromes, estrogens and salmon calcitonin are currently the only two drugs recommended by the U.S. Food and Drug Administration (USFDA) as safe and effective as treatment modalities in osteoporosis.

Journal Article↗
PubMed2000

The left ventricular assist device (LVAD). A bridge to heart transplantation.

Since its approval by the USFDA in 1998, the LVAD has been used primarily as a bridge to transplantation. It has been effective in improving the overall health and debilitated states in patients with cardiomyopathies and CHF by restoring them to a near normal hemodynamic state and improving end-organ blood flow. Recent studies indicate that the LVAD might be useful as a destination therapy, making transplantation unnecessary, providing one solution to the imbalance of heart donor supply to transplant candidate need.

Contraindications↗
PubMed2001

The initial United States experience with the ATS mechanical cardiac valve prosthesis.

From January 1, 1997 through June 30, 2000, 224 patients underwent valve replacement with the ATS Medical cardiac valve prosthesis under a USFDA-approved investigational device exemption study. Aortic valve replacement (AVR) was conducted in 152 patients (39 with coronary bypass) and mitral replacement (MVR) in 72 patients (18 with coronary bypass). Overall operative mortality was 1.8% (AVR = 2.8%, MVR = 0%), with only one valve-related death. In 372 patient-years of follow-up, there were an additional four patient deaths, two of which were valve related following a stroke. Valve-related complications included: thromboembolism (linearized rate = 3.8% per patient year), of which 3/11 had chronic deficits (0.8% per patient year); thrombosis (1 MVR = 0.8% per patient year); paravalvular leak (1 AVR = 0.4% per patient year); anticoagulant-related hemorrhage (1 AVR and 5 MVR = 1.6% per patient year) with no patient mortality; prosthetic valve endocarditis (1 MVR = 0.8% per patient year); and valve dysfunction (0%). Echocardiographic gradients were proportional to valve size and did not significantly change over the follow-up period. This study documented the ATS Medical prosthesis to be a valuable addition to the surgeon's armamentarium in the treatment of cardiac valvular disease.

Adult↗