Influence of pharyngeal airway respiration pressure on Class II mandibular retrusion in children: A computational fluid dynamics study of inspiration and expiration.

OBJECTIVES: To examine the influence of negative pressure of the pharyngeal airway on mandibular retraction during inspiration in children with nasal obstruction using the computational fluid dynamics (CFD) method. SETTING AND SAMPLE POPULATION: Sixty-two children were divided into Classes I, II (mandibular retrusion) and III (mandibular protrusion) malocclusion groups. MATERIAL AND METHODS: Cone-beam computed tomography data were used to reconstruct three-dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was simulated using CFD to calculate nasal resistance and pharyngeal airway pressure during inspiration and expiration. RESULTS: Nasal resistance of the Class II group was significantly higher than that of the other two groups, and oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups (P<.001). The oropharyngeal airway inspiration-expiration pressure difference in the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and Class III (0.68 Pa) groups (P=.006). CONCLUSION: Large negative inspiratory pharyngeal airway pressure due to nasal obstruction in children with Class II malocclusion may be related to their retrognathia.

Kinetics of Cd2+ in plasma, liver and kidneys after single intravenous injection of Cd-metallothionein-II.

To explore the kinetics of Cd2+ in the body, rats received a single intravenous injection of CdCl2 or Cd-saturated metallothionein-II at 0.3 mg Cd/kg body weight. Cd2+ in the two agents was biexponentially eliminated from plasma: rapidly in the first 5 min, and gradually later. Compared with CdCl2, Cd-saturated metallothionein-II showed lower Cd2+ concentrations in plasma during the first 30 min; larger values for parameters concerning distribution of Cd2+, its total body clearance and half-life time in the beta phase. Cd2+ uptake in the liver was higher with CdCl2, and, conversely, in the kidneys it was higher with Cd-saturated metallothionein-II. In Cd-saturated metallothionein-II, the renal content of Cd2+ reached a maximum (8 micrograms Cd2+/g tissue) on day 1, gradually decreasing thereafter; there was a higher area under the Cd2+ content-time curve, and a lower mean residence time of Cd2+; the kidneys showed severe necrosis and defluxion of proximal tubular cells at days 1 and 5, although there were regenerative and reversion signs on day 5. These findings suggested that, in the case of Cd-saturated metallothionein-II, Cd2+ being taken into the cells of proximal tubules was excluded predominantly due to cellular death and the resultant defluxion.

Transdermal absorption of L-dopa from hydrogel in rats.

To improve compliance in administration of l-dopa, transdermal absorption of the agent was investigated in rats in vitro employing two-chamber diffusion cells in which the excised rat abdominal skin was mounted, and in vivo using an alcoholic hydrogel containing l-menthol. The in vitro study revealed that in presence of l-menthol (2%, W/W), ethanol (20 and 40%, V/V) accelerated transdermal penetration of l-dopa with an increase of its percentages. The in vivo study showed that when the l-dopa-hydrogel containing 2% l-menthol and 40% ethanol was attached on the skin, plasma levels of l-dopa and norepinephrine increased with the time elapsed; the level of dopamine increased and reached a plateau thereafter; and the level of epinephrine was unchanged. These in vitro and in vivo findings indicated that the hydrogel formulation of l-dopa provides new direction in treating Parkinson's disease.

Biochemical aspects in the experimental barbital dependence IV--its effect on the hexokinase and phosphofructokinase activities in the rat brain.

Effects of barbital dosing on the neural hexokinase (EC 2.7.1.1) and phosphofructokinase (EC 2.7.2.11) activities in the rat, were examined. The barbital dependence in the rat was acquired by giving the barbital-admixed food. These two enzyme activities were investigated in the following three dissected portions of the brain: cerebral cortex, brain stem and cerebellum. The both enzyme activities in these three portions were depressed by the barbital dosing, while them being increased at the early stage of its withdrawal. From these results, it is considered that the measurements of hexokinase and phosphofructokinase activities probably give a possibility to estimate the degree of barbital dependence and its withdrawal, and that these two enzyme activities can be good indices in these conditions.

Biochemical aspects of pentylenetetrazole induced seizure.

At the onset of pentylenetetrazole induced convulsions, the adenylate cyclase activity and phosphodiesterase activity were increased. The former was markedly stimulated in the brain stem of rats. In the cerebral cortex and brain stem, the glucose level was significantly decreased, and the concentration of glucose-6-phosphate was increased. However, the definite changes in energy reserve system of the brain could not be observed at the onset of penetylentetrazole induced seizures. The present study revealed some correlation between pentylenetetrazole convulsions and the adenylate cyclase activity and glycometabolism.

Biochemical aspects of experimental barbital dependence III: effect on neural energy reserve system.

The effect of barbital intoxication on the neural energy reserve of rat was examined. The energy metabolism was depressed at dependent developing stage and recover to the non treated level at dependent stage. After withdrawal, rapid degradation of creatine phosphate and adenosine triphosphate was recognized. Later stage of withdrawal, the sum of creatine phosphate and adenosine triphosphate was decreased, and adenosine diphosphate and adenosine monophosphate was remarkably increased. These changes in neural energy reserve were parallel to the changes in adenylate cyclase activity and carbohydrate metabolism which were previously presented. These changes may have possible role in development of drug dependence and or withdrawal.

Intranephron distribution of purine-metabolizing enzymes in rats.

The activities of purine-metabolizing enzymes, 5'-nucleotidase, adenosine deaminase, and purine nucleoside phosphorylase in microdissected rat nephron segments were measured. The specific activity of 5'-nucleotidase was highest in the proximal tubules and the cortical collecting duct, but low in the glomerulus. In contrast, the highest activity of adenosine deaminase was found in the glomerulus. The distribution pattern of purine nucleoside phosphorylase was similar to that of adenosine deaminase. These results suggest that various nephron segments can form adenosine and that the glomerulus exhibits highest capacities to metabolize this nucleoside.

Biochemical aspects of experimental barbital dependence II: Effect on glycometabolism.

A single injection of barbital increased glycogen, while it decreased glucose and glucose-6-phosphate levels in the rat brain. In long barbital dosing (36 days), however, the metabolite level of carbohydrate was almost recovered to the non-treated level. At the later stage of withdrawal (24-48 hr), all metabolites examined except lactate decreased. Only lactate increased remarkably. The effect of barbital dosing and withdrawal was almost same in the three portions, i.e., the cerebral cortex, brain stem, and cerebellum. Barbital depresses the central glycometabolism, and at the dependent stage (long term barbital dosing, 36 days or more), metabolism was almost same as the control. At the later period of withdrawal, it appeared that lactate was increased because of the hypoxic condition caused by stroke. In conclusion, carbohydrate metabolism can probably serve as a sensitive measure for the development of barbital dependence and the onset of withdrawal.

Assay of ATPase and Na,K-ATPase activity using high-performance liquid chromatographic determination of ADP derived from ATP.

An HPLC assay for determination of ATPase activity was developed and validated. After stopping the enzyme reaction of the enzyme source (rat renal cortical basolateral membranes) with ATP, products derived from ATP were analyzed by two methods; HPLC determination of ADP derived from ATP, and colorimetry of inorganic phosphorus (Pi) released from ATP. This HPLC procedure was precise and linear over the range of protein amount of the enzyme source studied, and the intra-and inter-assay variations were lower than 10%. The values that were obtained by the two methods revealed a significant correlation. Also, even when the samples contained Pi or were contaminated with Pi, this HPLC method allowed determination of ATPase activity. In addition, when ouabain was used as an inhibitor, the HPLC method was found to be applicable for Na,K-ATPase determination. This indicated that this HPLC assay would enable determination of ATPases other than Na,K-ATPase, when other inhibitors are employed instead of ouabain.

[Effects of hexobendine on adenosine metabolism and myocardial energy metabolism (author's transl)].

To elucidate the mode of action of hexobendine, its effects on some enzyme activities, the uptake of adenosine by rat erythrocytes and changes in the concentration of various myocardial substrates following induced hypoxia in rat were studied. Hexobendine had no effect on the in vitro activities of the adenosine degrading enzyme, adenosine deaminase and of the A-PRTase, HG-PRTase which are associated with the salvage pathways of purine biosyntheses. The uptake of adenosine by rat erythrocytes in vitro was inhibited considerably by hexobendine. Hypoxic states results in a significant decrease in creatine phosphate, ATP, glycogen and glucose contents, and increase in ADP, AMP, adenosine and lactate contents in rat myocardials. These alterations in cardiac metabolism induced by hypoxia were significantly improved by hexobendine given orally in doses of 10 approximately 100 mg/kg. Thus, hexobendine was shown to maintain the normal aerobic energy metabolism of the heart under states of hypoxia. In such states adenosine may be released from tissues and this increase in the available concentration of adenosine in plasma through inhibition of uptake by erythrocytes may be involved in the coronary vasodilating action of hexobendine.

Mechanism of nephrotoxicity induced by repeated administration of cadmium chloride in rats.

To explore the mechanism of Cd nephrotoxicity, CdCl2 was subcutaneously injected to rats, at 3 mg Cd/kg body weight once a day, for 8 d. In the liver, Cd bound to metallothioneins (MTs-Cd) rose from d 1 after the initiation of CdCl2 administration, and reached a plateau after the administration ceased. In the plasma, MTs-Cd rose from d 4, peaked on d 8, and gradually fell thereafter. In the kidneys, leucine aminopeptidase (LAP) and N-acetyl beta-D-glucosaminidase (NAG) fell during d 6-20, and Cd bound to cellular membranes (Mem-Cd) rose from d 1 and reached a plateau during d 6-20. The Mem-Cd levels were significantly correlated with the reduction in the LAP and NAG activity; the values of MTs-Cd plus Mem-Cd were almost equivalent to those of total Cd. These findings showed that the hepatic synthesis of MTs-Cd occurred followed by its release into plasma; the extent of renal injury was aggravated as the plasma level of MTs-Cd rose; and a greater part of the renal Cd distributed intracellularly as the MTs-binding form, while the residual Cd distributed as the cellular membrane-binding form. Also, it was suggested that Cd that occurred as the cellular membrane- binding form in the kidneys was involved in manifestation of renal injury.

Transdermal absorption of L-dopa from a new system composed of two separate layers of L-dopa and hydrogel in rats.

To maintain the stability of L-dopa in hydrogel, a new system composed of two separate layers of L-dopa and hydrogel was developed. L-Dopa sheets were made by immersing L-dopa solution into wiper sheets and by lyophilizing them. Examination for stability of L-dopa in the L-dopa sheet revealed that its stability was maintained for at least 12 weeks, providing the sheet was kept at room temperature in a dark box. In a cutaneous absorption study of L-dopa in rats, an L-dopa sheet was attached to the shaved abdominal skin. A hydrogel composed of cutaneous absorption enhancers, water and ethanol, was spread on vinyl tape (hydrogel sheet), and this sheet was placed over the L-dopa sheet. L-Dopa that was administered transdermally effectively penetrated through the skin: The plasma level of L-dopa peaked at 30 min and remained high between 60 and 180 min after the cutaneous application. Our system, composed of two separated layers of L-dopa and hydrogel, enabled the stability of L-dopa to be maintained without losing transdermal absorption of L-dopa.

Effects of starvation on microsomal cytochrome P-450 and laurate-omega-hydroxylation of rat kidney and liver.

Cytochrome P-450 (P-450) content and laurate-omega-oxidation activity in rat kidney and liver microsomes were investigated following starvation. Multiple forms of P-450 were analyzed by one dimensional separation using peroxidase stained SDS-continuous gradient polyacrylamide gel electrophoresis. Gels of the hepatic microsomes treated with phenobarbital showed three P-450 bands, and the renal microsomes showed one sharp band, which was induced remarkably by starvation and coincided with the middle molecular form of P-450 from the hepatic microsomes. Since laurate-omega-oxidation activity was induced specifically by starvation but not by drug treatment, in both the kidney and the liver microsomes, the middle molecular form of P-450 might catalyze laurate-omega-oxidation. It seemed, therefore, that a special P-450 subunit catalyzing laurate-omega-oxidation has a greater function in the renal rather than hepatic microsomes because the specific laurate-omega-oxidation activity per starvation induced P-450 content was relatively similar in both the kidney and the liver.

Crystallization and preliminary X-ray diffraction studies of phospholipase D from Streptomyces antibioticus.

Phospholipase D (E.C. 3.1.4.4) from Streptomyces antibioticus has been crystallized in six crystal forms using the hanging-drop vapour-diffusion method. The type III and V crystals belong to monoclinic and hexagonal systems, respectively. All of the other crystal forms, types I, II, IV and VI, belong to orthorhombic space group P212121. Of these four types, the type VI crystals are suitable for X-ray structure determination. Crystal data for type VI crystals are: a = 50.1, b = 98.7, c = 107.6 A, V = 532100 A3, Z = 4 and Vm = 2.47 A3 Da-1. Type VI crystals diffract to at least 2.3 A resolution. A total of 11295 independent reflections to 3 A resolution have been collected from a type VI crystal using a conventional X-ray source, and its structural analysis is currently being conducted using isomorphous replacement methods.