Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis.

BACKGROUND: Some patients requiring acid suppression may be unable to take oral medications. AIM: To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients. METHODS: The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15. RESULTS: Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P < 0.001). CONCLUSIONS: Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications.

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole.

AIM: To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally. METHODS: Twenty-nine subjects received lansoprazole orally on days 1-7 and intravenous lansoprazole in NaCl on days 8-14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated maximal acid output were determined on days -1, 8, 9 and 15. Thirty-six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5. RESULTS: Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally. CONCLUSIONS: Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole.

In vitro evaluation of the Thermafil technique with and without gutta percha coating.

To determine the sealing ability of the Thermafil technique with and without gutta percha on the plastic carrier, 40 maxillary incisors were divided into four treatment groups: (A) Thermafil with gutta percha on the carrier; (B) Thermafil without gutta percha on the carrier; (C) lateral condensation with standardize gutta percha; and (D) a single standardized gutta percha cone. Average leakage in groups A-D were 0.64 mm, 1.32 mm, 0.53 mm, and 0.72 mm, respectively. The only significant difference was between the Thermafil without gutta percha and the other three groups (p < 0.05).

Effects of CO2 laser irradiation on tooth-root cementum.

With the aging of the American population and the endemic problem of gingival recession, patients will inevitably suffer from greater exposure of root surfaces and therefore will be more likely to develop root caries. The treatment of root caries is often frustrating. Traditional biomaterials used for the restoration of enamel caries have been less than satisfactory when margins of a cavity are adjacent to cementum. Although topical fluoride gels, toothpastes, and rinses have been used to prevent or to inhibit the development of root caries, there is a problem of access to the proximal surfaces. Consequently, the development of better methods to facilitate the prevention of root caries has become an important issue in dentistry.

Evaluation of glass ionomer as an endodontic sealant: an in vitro study.

This study investigated the sealing ability of glass ionomer as a root canal sealer with and without lateral condensation of gutta percha cones. Ten gutta percha cones were embedded in Grossman's sealer and 10 in glass ionomer sealer. The sealers were mechanically separated from the gutta percha. The cone surfaces were examined using scanning electron microscopy (SEM). SEM revealed a characteristic etch pattern on the glass ionomer group and a hybrid layer on the cone surfaces of the Grossman's group. Additionally, 40 maxillary incisors were divided into four treatment groups: 1) glass ionomer sealer with lateral condensation, 2) glass ionomer sealer with only one master cone, 3) Grossman's sealer with condensation, and 4) Grossman's sealer with only one master cone. The average values for leakage (mm) in groups 1 through 4 were 0.81 +/- 0.75, 4.30 +/- 1.82, 0.67 +/- 0.80, and 1.10 +/- 1.68, respectively. Statistical analysis showed that group 2 leaked more than the other three groups.

Dimensional stability of thermosensitive gutta-percha.

The expansion and shrinkage of four commercial brands of endodontic thermosensitive gutta-percha were evaluated. A modified volume dilatometry technique was used; the dilatometric system (DS) consisted of Pyrex glass capillary tubes and a specimen chamber. Each sample was weighed to 10(-4) mg, placed in the specimen chamber, and subjected to vacuum for 45 min to eliminate moisture or gases. The DS was gradually heated from 24 degrees C to 80 degrees C and then cooled to 24 degrees C using a well-agitated temperature-controlled water bath. In a parallel set of experiments, the DS was heated in the same manner but cooled to body temperature (37 degrees C) in the water bath and the temperature kept stable at 37 degrees C for 24 h. The level of the mercury meniscus within the DS was monitored to determine the percent volume change of each sample at 2 degrees C intervals. All samples expanded as the temperature was elevated and shrank during cooling. The percent volume change for each of the four gutta-percha products, as the temperature was raised to 80 degrees C, ranged from an expansion of +11.62 to +12.25. As the temperature was lowered from 80 degrees C to 24 degrees C, the percent volume change representing shrinkage ranged from -2.22 to -3.53. When the temperature was lowered from 80 degrees C to 37 degrees C, the products continued to exhibit shrinkage for a range of time between 45 min and 10 h before stabilizing at a fixed volume. The final percent volume change for each experiment, with each product, was positive, ranging from +5.50 to +7.20, with discernible differences between products.

Microscopic appearance of enamel white-spot lesions after acid etching.

Ultrastructural changes in surface characteristics of enamel white-spot lesions were compared with changes in the adjacent clinically sound enamel after they were etched with 30% phosphoric acid. Ten human permanent first molars exhibiting natural white-spot lesions were used as study specimens. The lesion surfaces and their adjacent sound enamel were etched with 30% phosphoric acid for 60 seconds. Specimens were then evaluated by polarized light microscopy, scanning electron microscopy, and energy-dispersive spectroscopy. The acid etching produced a porous surface on both the white-spot lesion and the surrounding sound enamel. However, the lesion surface appeared to be more resistant to acid and dissolved less than adjacent enamel. This difference in acid solubility produced a steplike appearance between a white-spot lesion and its adjacent enamel surface. Energy-dispersive spectroscopy demonstrated no difference in relative calcium-phosphorus ratios among the acid-etched white-spot lesion, acid-etched sound enamel, and unetched sound enamel.

Cyclic-AMP-responsive transcriptional activation of CREB-327 involves interdependent phosphorylated subdomains.

Cyclic AMP-regulated gene expression is mediated by specific phosphoproteins (CREBs) which bind to cAMP-responsive elements of gene promoters. By analyzing the transactivation activities and phosphorylations in vivo of deletion and point mutated chimeric fusion proteins of the placental CREB-327, in which the DNA-binding domain is replaced by the heterologous binding-domain of the yeast transcription factor GAL4, we localized the cAMP-responsive and phosphorylated domain to a minimal-essential sequence module of 46 amino acids (residues 92-137). This serine-rich, multiply-phosphorylated sequence consists of at least three interdependent subdomains required for transcriptional activation. Although phosphorylation of serine-119 by cyclic AMP-dependent protein kinase A is necessary for transcriptional activation, such activation requires both a phosphorylated heptadecapeptide domain located ten residues amino terminal to the serine-119 and an eleven-residue domain carboxyl terminal to the serine-119. Deletion of these two domains does not impair phosphorylation of serine-119. Further, deletion of the carboxyl-terminal domain does not alter phosphorylation of the heptadecapeptide domain. We propose that akin to the phosphorylation-dependent activation of enzymes, the transcriptional transactivation functions of CREB-327 involve a phosphorylation-dependent allosteric conformational mechanism.

Evidence for a cAMP-dependent nuclear factor capable of interacting with a specific region of a eukaryotic gene.

Nuclear extracts prepared from the livers of rats treated with or without 8-bromo-cAMP were tested for their ability to bind to various fragments from the flanking region of the gene encoding phosphoenolpyruvate carboxykinase (GTP) [GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32] known to contain the element that confers transcriptional regulation by cAMP. Using the nitrocellulose-filtration method, concentration-dependent, apparently saturable binding was seen that is both specific and cAMP dependent. Analysis of various fragments pinpointed the active binding region to positions within the -67 to -111 region, which coincides with the functional regulatory element as shown by recent transfection studies. Formation of an apparently single complex between a synthetic oligomer containing the region from -67 to -111 of the phosphoenolpyruvate carboxykinase gene and a factor in nuclear extracts from cAMP-treated rat liver was visualized by the gel-retardation method. Complex formation is both concentration and cAMP dependent and can be prevented by excess specific but not nonspecific competitor DNA. The congruity of the results with the two different methods suggests that the factor we have detected has properties consistent with a possible role as mediator of the transcriptional control exerted by cAMP in eukaryotic cells.

Evidence for reactive oxygen species inducing mutations in mammalian cells.

We have studied the mutagenicity (by selecting for mutants resistant to 6-thioguanine) and cytotoxicity (by determining cellular cloning efficiency) of physical and chemical agents in Chinese hamster ovary (CHO) cells, clone CHO-K1-BH4 (K1-BH4), and its radiation-hypersensitive transformant, AS52. AS52 cells contain a single functional copy of a bacterial gene, the xanthine/guanine phosphoribosyltransferase (gpt) gene instead of its mammalian equivalent, the hypoxanthine/guanine phosphoribosyltransferase (hprt) gene. We found that x-ray and neutron irradiations are equally toxic to both cell types; however, these physical agents are approximately equal to 10 times more mutagenic to AS52 cells than to K1-BH4 cells. Our earlier studies using Southern blot analysis showed that x-irradiation produces mostly or exclusively deletion mutations in both cell types. If reactive oxygen species mediate the mutagenic effects of radiations and chemicals, then radiomimetic compounds such as streptonigrin and bleomycin, which exert their biological effects via reactive oxygen species, and oxidizing compounds such as potassium superoxide and hydrogen peroxide should elicit a similar differential mutagenic response in both cell types. On the other hand, agents such as ethyl methanesulfonate, ICR 191, and UV light, which do not produce reactive oxygen species, should not elicit differential mutagenicity. Our results fulfill such predictions. The apparent hypermutability of AS52 cells probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants.