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At least 289 records · Page 16Linked to original sources
PubMed2007

Impact of antinucleants on transdermal delivery of testosterone from a spray.

The goal was to explore whether the incorporation of antinucleant polymers into a testosterone spray formulation could stabilize a putative supersaturated state and improve the delivery of the drug across the skin. Several antinucleants were screened using differential scanning calorimetry (DSC) and two candidates showed particular promise: a cyclodextrin derivative (RAMEB) and a vinylpyrrolidone/vinyl acetate copolymer (Kollidon VA64). These agents also improved significantly the long-term stability of saturated solutions of the drug. Further, using the method of mixed cosolvents, it was possible to create, in the presence of 5% w/v antinucleant polymer, supersaturated ethanol/propylene glycol/water (4:1:1 v/v) solutions of the drug with degrees of saturation between 1.4 and 2.6; however, these metastable systems existed only transiently under carefully controlled conditions and had reverted back to equilibrium solubilities of the drug within 6 h. When the same solutions were administered to hairless rat skin in vitro from mechanical sprays, no improvement in testosterone delivery, relative to a nonstabilized control, was observed. It appears, therefore, that the in situ crystallization process of the drug is more complex and incompletely understood (and cannot be predicted from DSC experiments). The complicated evaporation/volatilization process, which takes place when a spray is pulverized, requires better characterization before the use of supersaturation for testosterone delivery can be optimized.

Administration, Cutaneous↗
PubMed1981

Reversed-phase high-performance liquid chromatographic analysis of liothyronine sodium and levothyroxine sodium in tablet formulations: preliminary studies on dissolution and content uniformity.

Levothyroxine sodium was estimated from tablet formulations of levothyroxine sodium and liotrix (liothyronine sodium-levothyroxine sodium combination tablet). The procedures consisted of the addition of 3,3-,5-triiodothyronine as the internal standard to the pulverized sample, followed by an acidic butanol extraction, evaporation, and injection onto a muBondapak reversed-phase high-performance liquid chromatographic column. The eluent was methanol-water-phosphoric acid (50:50:0.1), and the effluent was monitored by UV detection at 254 nm. A standard linear calibration curve was obtained for direct standard solutions equivalent to 18-225 micrograms of levothyroxine sodium/tablet. The procedure is sensitive enough for single-tablet analysis. Using this procedure, content uniformity studies were performed on liothyronine sodium tablets, levothyroxine sodium tablets, and liotrix tablets. The procedure also was adapted for conducting dissolution studies on levothyroxine sodium tablets in deionized water using the rotating-paddle method.

Chromatography, High Pressure Liquid↗
PubMed1981

Simple high-performance liquid chromatographic assay for norethindrone--mestranol in combination tablets.

A simple, sensitive, and specific high-performance liquid chromatographic procedure was developed to assay norethindrone--mestranol combination tablets. The method involves a chloroform extraction of a single pulverized tablet. After centrifugation, and aliquot of the supernate was injected into a modular high-performance liquid chromatograph. The effluent from the silica column was monitored serially with a fixed-wavelength UV detector (254 nm) for norethindrone quantitation and a fluorescence detector (230 nm for excitation and 280 nm cutoff filter for emission) for mestranol quantitation. Progesterone was used as an internal standard. The method was employed successfully in content uniformity studies of several brands of commercially available tablets.

Chromatography, High Pressure Liquid↗
PubMed1984

High-performance liquid chromatographic assay for sodium levothyroxine in tablet formulations: content uniformity applications.

Sodium levothyroxine was quantitated in 25-300 micrograms/tablet formulations. The procedure consisted of pulverization of a suitable sample, extraction into acetonitrile-water (40:60, v/v) containing 0.05% o-phosphoric acid, and injection onto a bonded-phase cyanopropyl column; the effluent was monitored by UV detection at 225 nm. Spiked placebo recovery studies demonstrated the linearity of the method over the range of 80-120% of the label claim. Stability studies indicated that no degradation products or excipients interfered with the quantitation of the intact drug. Data demonstrating the accuracy and precision of this assay are presented, and the method was applied to the measurement of single-tablet content uniformity.

Chromatography, High Pressure Liquid↗
PubMed1984

Determination of minoxidil in bulk drug and pharmaceutical formulations by ion-pairing high-performance liquid chromatography.

An ion-pairing liquid chromatographic method with UV detection is described for the determination of minoxidil in bulk drug, compressed tablet, and topical solution formulations. The chromatographic system consists of a microparticulate octadecylsilica column and a mobile phase composed of sodium dioctylsulfosuccinate in aqueous methanol (pH 3). The bulk drug and the topical solution samples are prepared by the dissolution of the drug in internal standard solution. Sample preparation for the compressed tablet formulation involves dissolving the drug from an aliquot of pulverized sample and centrifuging to remove insoluble excipients. Quantitative recovery of minoxidil from formulation excipients was demonstrated; assay precision was less than 1% CV.

Chromatography, High Pressure Liquid↗
PubMed1988

Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions.

Solid dispersions of a poorly water-soluble drug [REV 5901; alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; 1] in an amphiphilic vehicle [Gelucire 44/14; 2] and in polyethylene glycol (PEG) 1000, PEG 1450, and PEG 8000 were prepared. The vehicle 2 was a mixture of hydrogenated fatty acid esters with a mp of 44 degrees C, and had a HLB value of 14. Compound 1 was dissolved or dispersed in molten vehicles at elevated temperatures. The pulverization and compression of solid dispersions were avoided by encapsulating the hot solutions directly into hard gelatin capsules. At room temperature, the dispersions solidified forming plugs inside the capsules. On storage, greater than 180 mg of 1 remained dissolved per gram of vehicle, while the excess drug formed fine crystals (less than 20 micron). When mixed with water, the dissolved drug separated as a metastable liquid. Due to the surfactant property of 2, the oily form of 1 that separated from this vehicle formed an emulsified system with a globular size of less than 1 micron, while greater than 80% of 1 that separated from the other three formulations coalesced to form large oily masses. As a result of the large difference in surface area, the dissolution rate of 1 in simulated gastric fluid from capsules containing 2 was much higher than that of a PEG-based formulation. The bioavailability (AUC) of 1 in dogs from capsules containing 2 was also higher than that from PEG 1000-based capsules.

Administration, Oral↗
PubMed1994

Newly discovered photodegradation products of nifedipine in hospital prescriptions.

New photodegradation products of nifedipine (1) have been isolated. They were found in tablets dispensed in the pulverized form by hospitals. 1 decomposed concurrently into six components after storage of 30 days under exposure to normal room light. The main photoproduct was a nitroso derivative (2) and others were minor. Preparative thin-layer chromatography has been used to isolate the six photodegradation products. The chemical structures of these isolated compounds were identified or estimated by comparison with authentic samples and/or using UV, IR, 1H NMR, mass spectroscopy, melting point determination, and elementary analysis. From these analyses, it was found that 1 was converted into a cis-azoxy derivative (4), a trans-azoxy derivative (5), a N,N'-dioxide derivative (6) and a lactam derivative (7) in addition to 2 and a nitro derivative (3). Furthermore, it is proposed that 2 is mainly responsible for the formation of these new products (4-7) by photochemical condensation.

Chromatography, High Pressure Liquid↗
PubMed2003

Morphological and cytogenetic analysis of intact oocytes and blocked zygotes.

We examined cytological and cytogenetic parameters of 1076 oocytes and 385 zygotes that failed to develop post in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Out of 1076 oocytes, 894 (83%) arrested oocytes showed a first polar body and were thus assumed arrested at metaphase II while the remainder showed no polar body. In the group of oocytes with a polar body, 20.5% had an abnormal karyotype. Cytologically, premature sperm chromosome condensation was noted in 28.3% of uncleaved oocytes. This high PCC can be explained by the different grades of oocyte maturity from one center to another. Oocytes from older women showed no increased aneuploidy but did show increased premature chromosome condensation. Analysis by classical technique of 220 uncleaved zygotes showed 91 with highly condensed chromosomes, 53 with asynchrony of condensation, 31 with pulverized chromosomes, and 45 arrested at the first somatic metaphase. Out of 385 arrested zygotes, 165 were explored by in situ hybridization. FISH using a set of 7 chromosome-specific probes showed aneuploidy in the chromosomes analyzed (13, 16, 18, 21, 22, X, Y) in 21.8% of blocked zygotes (19-25% depending on morphology). Extrapolating to other chromosomes, we expect that a vast majority of blocked zygotes and oocytes probably carry chromosome abnormalities. These data demonstrate the contributions of chromosome disorder in early embryo development blocking and implantation failure. Certainly, the issue of cytoplasm and nuclear immaturity and their relation to each other and to chromosome abnormalities provides a fertile area for future investigation in ART.

Adult↗
PubMed2006

Proteomic analysis of rice leaf, stem and root tissues during growth course.

Rice proteins were isolated from leaf, stem and root tissues, harvesting at 1, 2, 4, 8 and 10 weeks after budding. Each tissue of each age was separately pulverized in liquid nitrogen, and the resulted tissue powders were suspended in 10% TCA-acetone and followed by acetone suspension to precipitate at low temperature, which resulted in the tissue-specific and age-specific protein mixture. The protein mixtures were separated by 2-DE using polyacrylamide gels (26 x 20 cm). The protein spots were identified by N-terminal sequence analysis and by MALDI and LC-MS/MS analyses after in-gel tryptic digestion. From a total of 4532 spots, 676 unique proteins were identified, of which 80 proteins (12%) were observed in all three tissues: leaf, stem and root. In addition, 45 (7%) were common in leaf and stem, 57 (8%) in stem and root, and 10 (2%) proteins in root and leaf. Also 141 unique proteins (21%) were observed only for leaf, 96 (14%) for stem, and 247 (36%) for root tissue. Proteins playing a role for photosynthesis and energy production were most abundant in leaf and stem, and those for cell defense were rich in roots.

Amino Acid Sequence↗
PubMed2003

Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet.

Several studies have shown that notoginsenoides improve diastolic function in hypertensive subjects, induce the fibrinolytic system in in vitro models and act as antiproliferative agents on vessel leiomyocytes. Our aim was to evaluate their effect on fibrinogen and lipid plasma levels compared with a well-known HMGCoA reductase inhibitor. Seventy Wistar male adult rats on a fat-enriched diet were treated orally with P. notoginseng pulverized root (43 mg/kg/day or 86 mg/kg/day; 20 animals per group), fluvastatin (3 mg/kg/day; 20 animals) or physiological saline (5 mL/kg/day; 10 animals). The ten rats on a normocaloric diet were also treated with 5 mL/kg/day of physiological saline. After a 28-day treatment, the rats were killed and their blood analysed with standard procedures. Treatment with 43 mg/kg/day of P. notoginseng or 3 mg/kg/day of fluvastatin showed similar activity in decreasing total cholesterol (-23.70%, -19.29%, respectively) and triglycerides (-21.59%, -18.55%). The most evident effect of P. notoginseng was the reduction of fibrinogenaemia in treated rats compared with the control values (-38.10%; p < 0.001), no dose-relationship being shown in this effect. Moreover, no significant variation in HDL cholesterol and glucose levels was observed nor did relevant behavioural changes occur in association with the root intake. Besides a moderate, non dose-related decrease in the plasma lipid levels, P. notoginseng appeared to induce a significant reduction in the rat fibrinogenaemia.

Administration, Oral↗
PubMed2006

Potentials of ion trap collisional spectrometry for liquid chromatography/electrospray ionization tandem mass spectrometry determination of buprenorphine and nor-buprenorphine in urine, blood and hair samples.

A liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method has been developed for the analysis of buprenorphine (BUP) and nor-buprenorphine (NBUP) in biological fluids. Analytes are isolated from urine and blood, after addition of d4-buprenorphine (d4-BUP) as internal standard, by solid-phase extraction. Preparation of hair involves external decontamination, mechanical pulverization, overnight incubation in acidic medium, and neutralization prior to extraction. Enzymatic hydrolysis with beta-glucuronidase may be performed to distinguish between free and total BUP. Chromatographic separation is accomplished by gradient elution on a cyanopropyl 2.1 x 150 mm column. Positive ion ESI and MS analyses are carried out in an ion trap mass spectrometer. The use of this mass analyzer allows effective collisional experiments to be performed on ESI-generated MH+ species. Abundant product ions are produced, which can be monitored together with precursor ions without losing sensitivity. Thus, assay selectivity is definitely increased with respect to LC/ESI-MS/MS methods in which only precursor ions are monitored. The method has good linearity (calibration curves were linear in the range 0.1-10 ng/mL in urine and blood, in the range 10-160 pg/mg in hair) and limits of detection of 0.05 ng/mL for both BUP and NBUP in blood and urine samples, of 4 pg/mg for both analytes in hair. Both intra- and inter-assay precision and accuracy were satisfactory at three concentrations studied: relative standard deviations were <13.7% in urine, <17.3% in blood, <17.8% in hair; percent deviation of the mean from the true value was always <10.5% in urine and blood, <16.1% in hair. The method can be used to determine both analytes in the urine and hair of drug addicts on replacement therapy, and in post-mortem blood specimens when there is suspicion of drug-related death.

Analgesics, Opioid↗
PubMed2002

A multivalent assay to detect glycosaminoglycan, protein, collagen, RNA, and DNA content in milligram samples of cartilage or hydrogel-based repair cartilage.

The biochemical measure of success in assisted cartilage repair is normally judged by repair tissue cell density, mRNA and protein expression, and accumulation of extracellular matrix molecules. Existing methods to solubilize cartilage matrix proteoglycans and cellular DNA for quantification, such as papain digestion, often destroy one or more species of the above-named parameters, in order to render others measurable. We have therefore developed a methodology to measure specific levels of mRNA, protein, DNA, glycosaminoglycan, and collagen content on single pulverized 10-mg samples of cartilage, or tissue-engineered cartilage, using successive extractions in concentrated guanidine hydrochloride (GuCl) and guanidine thiocyanate (GITC) solutions. Conditions were developed to solubilize most cellular proteins, DNA, proteoglycans, and some matrix proteins with an initial GuCl extraction step. A subsequent extraction with GITC was essential to solubilize the majority of the cellular RNA. Guanidine-insoluble material was rendered soluble by papain digestion, to enable quantification of collagen, residual glycosaminoglycan, and residual unextracted DNA in individual samples. In general, total collagen, GAG, and DNA content measured in multivalent-extracted samples was similar to that obtained with samples digested directly with papain. Moreover, we were able to reliably detect, in these same multivalent extracts, expressed mRNA as well as specific cellular and extracellular matrix proteins. This multivalent assay could be applied to a variety of cells cultured in biopolymers and to tissues from which biochemical components may be otherwise difficult to extract.

Animals↗
PubMed2000

Centrosome alterations induced by formamide cause abnormal spindle pole formations.

The formation of the bipolar mitotic apparatus depends on accurate centrosome organization which is crucial for the separation of the genome during cell division. While it has been shown that mutations and overexpression of centrosome proteins (Brinkley and Goepfert, 1998; Pihan et al., 1998) can cause abnormal spindle pole formation, here we report that damages to centrosome structure caused by the chaotropic agent formamide will cause multipolar mitoses upon recovery from the effect when applied at first cell division in sea urchin eggs. Formamide was used as a chemical tool to manipulate centrosome structure and to investigate the effects on microtubule organization. When 1-1.5 m formamide was administered for 30 min at prometaphase of first cell division, microtubules were disassembled and centrosomes compacted into dense spheres around highly condensed chromatin. Upon recovery from formamide, centrosomes decompacted and attempted to form various mitotic organizations. Normal recovery (and attempts of recovery) to bipolarity was possible in five percent of cells treated with 1-1.5 m formamide for 30 min, but abnormal patterns of spindle formation were observed in all other cells, which included mono- (20%), tri (45%), and multipolar (30%) formations organized by mono-, tri-, and multipolar centrosome clusters. When cells were treated with 1.5 m formamide for 90 min, centrosomes became pulverized and fragmented and only monopolar mitotic formations were observed upon recovery. These results are highly reproducible and reveal that abnormalities in centrosome structure can lead to abnormal mitosis which is not caused by mutation or overexpression of centrosome proteins.

Animals↗
PubMed1999

Gap junctions containing alpha8-connexin (MP70) in the adult mammalian lens epithelium suggests a re-evaluation of its role in the lens.

A missense mutation in one of the three lens connexins, alpha8-connexin, has been recently shown to be the genetic basis of the zonular pulverant lens cataract. This connexin had been considered to be expressed only in lens fibre cells. The present studies show that alpha8-connexin is also expressed in the lens epithelial cell layer. For this study, the distribution of gap junctions in the adult bovine lens has been investigated by confocal immunofluorescence microscopy using antibodies against alpha8-connexin (MP70) and alpha1-connexin (Cx43). In addition to the anticipated localisation of alpha8-connexin to the broad faces of lens fibre cells as reported in other species, alpha8-connexin was also found colocalized with alpha1-connexin at plaques in the lateral epithelial-epithelial plasma membranes of the bovine lens. These data suggest that mixed alpha8-connexin/alpha1-connexin plaques are between epithelial cells at their apico-lateral plasma membranes, rather than between epithelial and fibre cells. Indeed, freeze fracture analyses of the epithelial-fibre cell interface failed to reveal gap junctions connecting the epithelium and the underlying fibre cells. Importantly, microdissection and subsequent immunoblotting of lens epithelium samples confirmed the immunolocalisation results. The data suggest mature mammalian lens epithelial cells could form either heteromeric, heterotypic and/or mixed homomeric-homotypic gap junctional complexes with unique physiological properties, an important point when considering the role of epithelial cell connexins in cataractogenesis.

Animals↗
PubMed1999

Atomic force microscopy study of tooth surfaces.

Atomic force microscopy (AFM) was used to study tooth surfaces in order to compare the pattern of particle distribution in the outermost layer of the tooth surfaces. Human teeth and teeth from a rodent (Golden hamster), from a fish (piranha), and from a grazing mollusk (chiton) with distinct feeding habits were analyzed in terms of particle arrangement, packing, and size distribution. Scanning electron microscopy and transmission electron microscopy were used for comparison. It was found that AFM gives high-contrast, high-resolution images and is an important tool as a source of complementary and/or new structural information. All teeth were cleaned and some were etched with acidic solutions before analysis. It was observed that human enamel (permanent teeth) presents particles tightly packed in the outer surface, whereas enamel from the hamster (continuously growing teeth) shows particles of less dense packing. The piranha teeth have a thin cuticle covering the long apatite crystals of the underlying enameloid. This cuticle has a rough surface of particles that have a globular appearance after the brief acidic treatment. The similar appearance of the in vivo naturally etched tooth surface suggests that the pattern of globule distribution may be due to the presence of an organic material. Elemental analysis of this cuticle indicated that calcium, phosphorus, and iron are the main components of the structure while electron microdiffraction of pulverized cuticle particles showed a pattern consistent with hydroxyapatite. The chiton mineralized tooth cusp had a smooth surface in an unabraded region and a very rough structure with the magnetite crystals (already known to make part of the structure) protruding from the surface. It was concluded that the structures analyzed are optimized for efficiency in feeding mechanism and life span of the teeth.

Acids↗
PubMed1994

Extracorporeal shock-wave lithotripsy prior to laparoscopic cholecystectomy. Does it make sense?

The extraction of large gallstones in laparoscopic cholecystectomy either requires the enlargement of one of the incisions or intraoperative lithotripsy. Preoperative extracorporeal shock-wave lithotripsy (ESWL) might theoretically solve the problem and facilitate the extraction of the gallbladder. Ten patients with at least one gallstone larger than 20 mm in diameter underwent ESWL treatment within 24 h prior to laparoscopic surgery. Complete pulverization of stones was achieved in one patient. Fragmentation into pieces smaller than 10 mm could be observed in another three cases. Additional mechanical fragmentation employing forceps was necessary in seven and an enlargement of the incision in five of the 10 patients. Compared to a matched group of 10 control patients with gallstones of corresponding size receiving mechanical lithotripsy, the ESWL did not show an advantage, but rather an increase in costs. It therefore cannot be recommended.

Adult↗
PubMed1975

Derivative chromosomal structures from a ring chromsome 4.

This report describes the results from cultured lymphocytes studied at metaphase, anaphase, and interphase from an individual with a ring chromosome 4. A ring was present in 90.1% of metaphases. Special attention was directed towards the occurrence of derivative chromosomal structures, such as partially duplicated and triplicated rings, tricentric rings, chains of 3 interlocked rings, rod-shaped chromosomes, "pulverized" rings, and others. The clinical features of the individual (small stature and impaired mental development, hypoplastic thumbs, ptosis palpebrae hypoplastic external male genitalia, abnormal dermatoglphic pattern) did not conform to a specific phenotype.

Blood Group Antigens↗
PubMed1983

Cell cycle-specific changes in the ultrastructural organization of prematurely condensed chromosomes.

Prematurely condensed chromosomes (PCC) of HeLa cells synchronized in different phases of the cell cycle were analyzed by high-resolution scanning electron microscopy. The purpose of this study was to examine changes in the arrangement of the basic 30-nm chromatin fiber within interphase chromosomes associated with progression through the cell cycle. These studies revealed that highly condensed metaphase chromosomes and early G1-PCC consisted of tightly packed looping fibers. Early to mid G1-PCC were more extended and exhibited gyres suggestive of a despiralized chromonema. Further attenuation of PCC during progression through G1 was associated with a gradual transition from packed looping fibers to single extended longitudinal fibers. This process occurs prior to the initiation of DNA synthesis which appears to be localized within single longitudinal fibers. Following replication of a chromosome segment, extended longitudinal fibers were rapidly reorganized into packed looping fiber clusters concomitant with the formation of a multifibered chromosome axis. This results in the characteristic "pulverized" appearance of S-PCC when viewed by light microscopy. Subsequently, adjacent looping fiber domains coalesce, resulting in the uniformly packed, looping fiber arrangement observed in G2-PCC. Spiralization of the chromonema during the G2-mitotic transition results in the formation of highly compact metaphase chromosomes.

Cell Cycle↗