Glandular odontogenic cyst: a case report and literature review.
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Diagnosis, Differential↗
Biomedical subjects
E Nakashima
Publications and source records attributed to E Nakashima.
Relationship of five anthropometric measurements at age 18 to radiation dose among atomic bomb survivors exposed in utero.
Five body measurements--standing height, body weight, sitting height, chest circumference and intercristal diameter--of 18-year-old atomic bomb survivors exposed in utero in Hiroshima and Nagasaki were analyzed in relation to DS86 uterine dose. Age in utero was divided into four periods: 0-7, 8-15, 16-25 and > or = 26 weeks. This categorization is based upon the study of radiation-induced brain damage. The linear regression analyses for these five variables showed significant decreases with increasing dose. The regression coefficients were -2.65 cm/Gy for standing height, -2.46 kg/Gy for body weight, -0.92 cm/Gy for sitting height, -1.37 cm/Gy for chest circumference and -0.32 cm/Gy for intercristal diameter. The multivariate test statistic for the overall dose effect on five body measurements was significant, but the interaction between dose and gestational period was not significant. Principal-component analysis was applied to the five variables. For the first-component scores, the dose effect was significant, but the interaction between dose and gestational period was not significant. For the second-component scores, the dose effect was significant specifically at 0-7 weeks. The radiation dose effect on the second principal component found at 0-7 weeks of gestation suggests that malformations occur in this period.
Adolescent↗
Pharmacokinetics of anticholinergic drugs and brain muscarinic receptor alterations in streptozotocin diabetic rats.
We studied the effects of experimental diabetes on the pharmacokinetics of biperiden (BP) and scopolamine (SP) and brain muscarinic receptor alterations in rats after the injection of streptozotocin (STZ) (60 mg kg-1 i.v.). The serum levels of BP and SP differed significantly between the rats 14 weeks after the STZ treatment and age-matched control rats. The values of total body clearance (CLtot) of BP and SP were significantly increased by STZ treatment. The values of volume of distribution (Vdss) of SP were slightly increased in the STZ-treated rats, although Vdss of BP was decreased. Because of the high lipophilicity of BP, Vdss of BP may be decreased due to the reduced fat tissue volume caused by STZ treatment. The density of the muscarinic receptors in whole brain was measured by a radioligand receptor binding assay using [3H]-quinuclidinyl-benzylate ([3H]-QNB). The density in the diabetic rats two weeks after the STZ treatment was significantly decreased compared to age-matched control rats. However in the diabetic rats 14 weeks after the STZ treatment, there was no difference in the density of muscarinic receptors. The IC50 of muscarinic antagonist for the binding of [3H]-QNB to the receptor did not change on STZ treatment. Modulation of the receptor following repeated anticholinergic drug exposure was studied. In control rats, the number of muscarinic receptors in the brain increased by 6.9% on chronic treatment with BP for two weeks. When diabetic rats were treated with BP and SP, the number of muscarinic receptors in the brain increased by 9.6% and 33.8%, respectively.
Animals↗
Frequency of reciprocal translocations and dicentrics induced in human blood lymphocytes by X-irradiation as determined by fluorescence in situ hybridization.
This study was designed to test the scoring efficiency of reciprocal translocations and dicentrics induced by X-irradiation in vitro using the fluorescence in situ hybridization (FISH) technique. An excess was found in the frequencies of reciprocal translocations relative to those of dicentrics by measurement with FISH at the first cell division after irradiation (translocation:dicentric approximately 60:40). However, when the same metaphases were also evaluated sequentially by a conventional staining method, the ratio of about 50:50 was restored. This was due in part to misclassification of certain dicentrics as reciprocal translocations by the FISH technique.
Adult↗
Brain regional pharmacokinetics of biperiden in rats.
The pharmacokinetic profiles of biperiden (BP) in blood and in specific brain regions were investigated in rats after acute i.v. administration. The regional brain-to-blood unbound concentration ratios (Kpf) were also determined after 16 h intravenous infusion of BP. The Kpf values ranged from 30 to 75 in the different brain regions and showed decreasing concentrations in the following order: pons + medulla oblongata, basal ganglia, amygdala, hypothalamus, thalamus, mesencephalon, bulbus olfactorius + septum, hippocampus, frontal cortex, occipital cortex, cerebellum. The relationship between BP and acetylcholine (ACh) concentrations in the brain regions was examined. ACh levels in the various brain regions ranged from 8 to 44 ng g-1 tissue. There was a significant correlation between the Kpf values of BP and the levels of ACh in the brain regions except for the pons + oblongata. BP concentrations in the brain regions after BP administration were predicted based on the physiological pharmacokinetics. There was reasonable agreement between the model predictions and the observed data.
Acetylcholine↗
Variable glyceryl dinitrate formation following infusions of glyceryl trinitrate at different vascular sites in the rat.
The availability of glyceryl trinitrate (GTN) and the differential formation of dinitrate metabolites (GDNs) in various organs as a function of routes of administration were investigated in the rat. GTN was infused at 2.0 micrograms/min via the left femoral vein (LFV), left external jugular vein (LJV), left femoral artery (LFA), and hepatic portal vein (HPV). Blood concentrations of GTN and GDNs were measured in femoral arterial samples. Different infusions yielded GTN steady-state concentrations in the following rank order: LJV greater than or equal to LFV greater than LFA greater than or equal to HPV. Furthermore, the GDN formation ratios (1,2-GDN/1,3-GDN) are different: LFV greater than LJV greater than LFA greater than HPV. The availabilities of GTN through the leg, vein, and liver were derived. GTN is significantly extracted and metabolized in these organs, and the leg and the vein prefer 1,2-GDN formation, while the liver forms 1,3-GDN predominantly.
Animals↗
Relationships in the structure-tissue distribution of basic drugs in the rabbit.
The relationship between the tissue-to-plasma partition coefficients (Kp) and drug lipophilicity was investigated using highly lipophilic drugs with apparent partition coefficients of 150 or above in an octanol-water system at pH 7.4. Ten clinically popular basic drugs with different dissociation coefficients (pKa) and lipophilicity were used. The Kp values were determined in nondisposing organs after the i.v. administration of individual drugs in rabbits. The free fraction in plasma and the blood-to-plasma concentration ratio were determined in vitro. Then the tissue-to-plasma ratios of nonionized and unbound drug concentrations (Kpfu) were calculated from Kpf (ratio of unbound drug). The true octanol-water partition coefficient of the nonionized drugs (P) was used to analyze the Kpf and Kpfu. In all tissues, log Kpfu was more highly correlated with log P than log Kpf.
Animals↗
Pharmacokinetics of nitroglycerin and its dinitrate metabolites over a thirtyfold range of oral doses.
The pharmacokinetics of nitroglycerin and the formation of its dinitrate metabolites (1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate) were determined in six healthy volunteers after administration of six oral solution doses ranging from 0.4 mg to 13 mg. ANOVA analysis indicated significant differences between subjects for all Cmax/dose and AUC/dose measurements. No significant difference between doses were noted for these parameters except for AUC/dose for 1,3-glyceryl dinitrate. The ratio of metabolites (1,2-metabolite/1,3-metabolite) for the 0.4 mg dose was significantly different from the ratios for the doses of 1.6 mg or higher. Measurements of the combined residence time parameter suggest nonlinearity in nitroglycerin absorption and metabolism processes of AUMC/AUC between the 0.4 and the 13 mg doses. Consistent results were observed in the AUC ratios of metabolites for 0.4 mg doses of nitroglycerin between oral and sublingual administrations, suggesting that the increased metabolite ratio noted for sublingual nitroglycerin may reflect differences in dose, rather than differences in route of administration.
Administration, Oral↗
An integrated approach to pharmacokinetic analysis for linear mammillary systems in which input and exit may occur in/from any compartment.
The general treatment of linear mammillary models employing input and disposition functions and Laplace transforms is expanded to solve concentration-time equations AUC and AUMC in any compartment without restricting sites of input or output. In this integrated approach to noncompartmental pharmacokinetic analysis, the values of AUC and AUMC can be calculated from Laplace transforms with some very simplified treatments. Tables of input functions, disposition functions, Laplace transforms, and derivatives of the Laplace transforms are presented. The relationships between the integrated parameters and various mammillary model parameters are presented using several examples.
Linear Models↗
Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts.
So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration-time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P less than 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The Vss value (liter) for tobramycin was predicted by using the equation 0.261 . (ideal body weight (kg) + 0.4 . [total body weight (kg) - ideal body weight (kg)]). The Vss value of cefazolin was predicted to be 0.3 . (predicted Vss of tobramycin) + 0.052 . total body weight (kg). A good correlation between the predicted and the observed Vss values was obtained.
Blood Proteins↗
Kinetics of peritoneal drug transport in rats: an application of the pore theory of transcapillary exchange.
In order to quantitatively describe the peritoneal transport of drugs, this paper proposes a kinetic model that is based on the hydrodynamic pore theory of transcapillary exchange, and incorporates an explicit description of volume and osmolality changes in the dialysate. Sulfisoxazole (SIX) and benzoic acid (BA) were used as model compounds. Following intraperitoneal administration of dialysate in rats, the osmolality, volume, and drug concentration in the dialysate were measured with respect to time. The obtained data were analyzed to give hydrodynamic parameters for solvent and a solute (including drug) by a computer-aided curve-fitting procedure according to the differential equations derived from the model. The present method, requiring no approximation of the changes in dialysate volume, made it possible to predict the concentration profiles of BA under different initial conditions of dialysate (i.e., different osmolality and volume). Solvent drag effect contributed little to the peritoneal transport of SIX and slightly to that of BA. It was also found that the peritoneal transport of BA is blood-flow limited while that of SIX is diffusion limited.
Animals↗
Peritoneal transport of beta-lactam antibiotics: effects of plasma protein binding and the interspecies relationship.
In order to examine quantitatively the effect of plasma protein binding on the peritoneal transport of beta-lactam antibiotics, we employed a kinetic model based on the pore theory of transcapillary exchange. This model incorporates the changes in the volume, osmolality, and antibiotic concentration in the dialysate, so that the apparent capillary membrane permeability (Pd) and the reflection coefficient (sigma d) of an antibiotic could be assessed. Six cephalosporins (cefatrizine, cefazolin, cefpiramide, ceftazidime, ceftriaxone, cephaloridine) were used as model compounds. While the unbound fractions of these antibiotics ranged widely from 0.08 to 0.57, including linear and nonlinear protein binding, the concentration-time profiles in plasma and the peritoneal dialysate after intravenous administration in rats could be interpreted well by our model, assuming that only the unbound antibiotic is available for the peritoneal transport. The estimated Pd values were almost the same among the drugs examined. Moreover, the Pd values of cefazolin in mice, rats, and rabbits exhibited a 0.83-power dependency on the animal body weight, indicating that Pd is significantly related to the peritoneal surface area. On the other hand, the sigma d values of cefazolin were found to be almost the same among the animal species examined. Finally, the concentration-time profile of cefazolin in the dialysate after intravenous administration in a patient with end-stage renal failure was successfully predicted using the Pd value extrapolated from those of the experimental animals.
Aged↗
Interindividual changes in volume of distribution of cefazolin in newborn infants and its prediction based on physiological pharmacokinetic concepts.
The purpose of this study was to investigate factors affecting the volume of distribution of cefazolin (a beta-lactam antibiotic) in newborn infants with bacterial infections, and to propose a method for predicting the volume of distribution at steady state per body weight (Vdss/BW). Cefazolin and tobramycin (an aminoglycoside) were simultaneously given to newborn infants (aged 2 to 28 d), and plasma concentration-time data were analyzed on the basis of model-independent moment analysis. The Vdss/BW values ranged from 0.212 to 0.373 L/kg for cefazolin and from 0.384 to 0.541 L/kg for tobramycin. The unbound fraction of cefazolin in plasma (fp) fluctuated widely, from 0.22 to 0.83, among patients. The Vdss/BW value for cefazolin was characterized by both large extracellular water volume and a remarkable change in fp, and could be predicted as a function of fp using physiological pharmacokinetic concepts. Moreover, interindividual changes in the unconjugated bilirubin:albumin molar ratio were predominantly responsible for the individual variation in the fp values of cefazolin in newborn infants.
Blood Proteins↗
General treatment of mean residence time, clearance, and volume parameters in linear mammillary models with elimination from any compartment.
A general treatment for mean residence time, clearance, and volume parameters in linear mammillary models which includes the possibility of first-order elimination from compartments other than the central compartment is presented. The interrelationship between noncompartmentally derived parameters and compartmentally derived pharmacokinetic microconstants is described. The concept of exit site dependent and exit site independent parameters is introduced in the development of these treatments. Explications of mean residence time in terms of elimination rate, amount eliminated, and amount in the body are presented together with demonstrations of their utility.
Humans↗
Kinetic analysis of the peritoneal transport of quinolonecarboxylic acids in rats.
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Animals↗
Effects of fasting on biperiden pharmacokinetics in the rat.
The effects of fasting on the pharmacokinetics of biperiden in rats were examined. Total clearance of biperiden was greater than 90% ascribable to hepatic clearance and was essentially blood-flow dependent. The number of compartments in the preferred pharmacokinetic model of biperiden changed from three (for normal rats) to two (for fasted rats). The smaller mean residence time (MRT) values found for fasted rats were attributable to decreases in distribution volume. Biperiden showed much higher lipophilicity than haloperidol, thiopental, and hexobarbital, and its tissue-to-plasma partition coefficient in adipose tissue was 20-fold higher than that in muscle. The influence of changes in volumes of adipose tissue and muscle on distribution volume (Vdss/BW) was evaluated from tissue-to-plasma partition coefficients. The value of Vdss/BW was predicted to decrease with decrease of adipose tissue, and to increase with decrease of muscle tissue. These results suggest that the observed decrease of Vdss/BW in fasted rats reflects reduced capacity to trap biperiden in the body, especially in adipose tissue. Possible clinical implications of these results are discussed.
Adipose Tissue↗
Transdermal bioavailability and first-pass skin metabolism: a preliminary evaluation with nitroglycerin.
A model comprising six compartments, a systemic and presystemic compartment for nitroglycerin and each of its two dinitrate metabolites is presented to describe the interrelationships between plasma concentrations of the two metabolites and metabolism in skin after intravenous and transdermal ointment administration of nitroglycerin. Using a perfusion-limited pharmacokinetic model, the equation for the calculation of the fraction (F) of the dose of nitroglycerin systemically available from skin was derived independent of nitroglycerin plasma concentrations. Estimated F values (0.68-0.76) are comparable to values reported in Rhesus monkeys (0.80-0.84). Simulated plasma concentration-time profiles were reasonably fitted to the observed concentrations of nitroglycerin and its two metabolites after transdermal administration. This preliminary model suggests that transdermal bioavailability for a drug metabolized in the skin can be reasonably estimated.
Administration, Cutaneous↗
Saturable uptake of cefixime, a new oral cephalosporin without an alpha-amino group, by the rat intestine.
The mechanism of intestinal uptake of cefixime, a new oral cephalosporin antibiotic, has been examined using the everted jejunum of rats. The initial uptake rates were apparently pH-dependent with the maximum rate at pH 5.0 and a 3-fold reduction at pH 7.0. The uptake at pH 5.0 followed mixed-type kinetics involving saturable and non-saturable processes in a manner similar to that for several amino-beta-lactam antibiotics. Cefixime uptake was inhibited significantly by 20 mM permeants such as cyclacillin, cephradine, benzylpenicillin, propicillin, glycyl-L-proline and glycyl-glycine. Replacement of Na+ in the medium with choline produced a slight but significant inhibition of cefixime uptake. In spite of the absence of significant inhibition by the amino acids glycine and proline, the dipeptide, glycyl-L-proline in Na+-free medium showed a marked inhibitory effect. The inhibition kinetics of cefixime uptake by glycyl-L-proline and cyclacillin were consistent with competitive-type inhibition. This study provides the first evidence of saturable intestinal uptake of a cephem antibiotic without an alpha-amino group in the side chain, suggesting transport through the dipeptide carrier system(s).
Animals↗