Study of pharyngeal airway morphology with CBCT: Benefits of four premolar extraction orthodontic treatments.

Background and Aim: Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a controversy. Patients and Methods: Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests. Results: In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly. Conclusion: Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.

Intragastric vs intraintestinal viscous polymers and glucose tolerance after liquid meals of glucose.

To determine whether viscous fibers improve glucose tolerance by slowing gastric emptying or impeding intestinal uptake of glucose, 800 mL of 0.2 mol glucose/L were instilled into the stomachs of the dogs and allowed to empty from the stomach out the proximal limb of a duodenal fistula while simultaneously fresh solution was instilled into the distal duodenum at the same rate. This technique allowed us to study 33 g pectin/L, isoviscous 400 g PEG 20,000/L, or 11 g guar/L when present with glucose in the stomach only, the intestine only, or in both stomach and intestine. Rates of gastric emptying and plasma glucose were lower when viscous polymer was present at both sites than at either site separately. Slowing of gastric emptying was an interactive outcome of viscosity at both loci, probably from slowed intestinal absorption of glucose with its exposure to more intestinal sensors. Reductions in postcibal glucose concentrations depended on slowing of both gastric emptying and intestinal absorption.

Discovery of 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, an orally active, non-nucleoside adenosine kinase inhibitor..

Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic and antiinflammatory actions of ADO. Optimization of the high-throughput screening lead, 4-amino-7-aryl-substituted pteridine (5) (AK IC(50) = 440 nM), led to the identification of compound 21 (4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido [2,3-d]pyrimidine, ABT-702), a novel, potent (AK IC(50) = 1.7 nM) non-nucleoside AK inhibitor with oral activity in animal models of pain and inflammation.

Factors that affect the performance of lipase on fat digestion and absorption in a canine model of pancreatic insufficiency.

In a previous experiment, absorption of [14C]triolein was poor under low lipase in the first postcibal hour during which luminal conditions change markedly. We wondered how low lipase might be affected by changing concentrations of fat, bile salts, titratable acid, pepsin, and food particles. Therefore, in dogs with duodenal and midintestinal fistulas, endogenous bile and pancreatic juice were excluded from the intestinal lumen and replaced with varied amounts of exogenous bile and pancreatic enzymes during steady perfusions. Oil emulsions contained [14C]triolein and [3H]glycerotriether. A double isotope ratio method and a double isotope, double extraction method were used to determine, respectively, the amount of [14C]triolein absorbed and hydrolyzed by the midgut. Lipolysis increased with both substrate and enzyme inflows, whether inflows were varied by changing concentrations or rates of volume flow. But at increasing rates of fat entry, the percent of fat hydrolyzed by the midgut declined. Neither pH 4 nor 5 citrate affected fat hydrolysis or absorption when titratable acid was infused at rates < or = 16 mEq/h; but pepsin reduced both. Whereas meat particles bound lipase, their presence augmented lipolysis. We speculate that rapid gastric emptying of fat and peptic deactivation of duodenal lipase were the main factors responsible for the previously poor performance of low lipase in the first postcibal hour.

Effect of replenished lipase on postcibal absorption of fat in a canine model of pancreatic insufficiency.

Clinical studies indicate that as little as 10% of pancreatic secretory capacity is needed to ensure normal digestion; but we found previously that supplying lipase to the postcibal duodenum at > or = 10% of normal rates did not normalize fat absorption in pancreatic insufficiency. Therefore, we examined the dose-response of endogenous lipase on fat absorption. Pancreatic juice was excluded and returned in varied amounts to the postcibal duodenum in dogs with pancreatic fistulas. Meals contained margarine labeled with digestible [14C]triolein and indigestible [3H]glyceroltriether. With an isotope ratio method, we estimated the amount of radiotriolein absorbed hourly from chyme collected for 6 h after a meal from midgut fistulas. When all pancreatic juice was excluded, there was almost no absorption. When 10 or 20% of pancreatic juice was returned, approximately 80% of triolein was absorbed by the midgut, compared with 90% absorption when all pancreatic juice was instilled. However, we observed that at 10 and 20% replenishments, the amount of triolein absorbed in the first hour was much less than in subsequent hours, and thus that absorptive efficiency varied with the fraction of fat emptied from the stomach during the first hour. At rates of 10 or 20% of normal, lipase was equally effective, whether from endogenous juice or exogenous pancreatin.

Specific absorption rates and induced current distributions in an anatomically based human model for plane-wave exposures.

We have previously reported local, layer-averaged, and whole-body-averaged specific absorption rates and induced currents for a 5,628-cell anatomically based model of a human for plane-wave exposures 20-100 MHz (Chen and Gandhi 1989). Using a higher resolution, 45,024-cell model of the human body, calculations have now been extended to 915 MHz using the finite-difference time-domain method. Because of the higher resolution of the model, it has been possible to calculate specific absorption rates for various organs (brain, eyes, heart, lungs, liver, kidneys, and intestines) and for various parts of the body (head, neck, torso, legs, and arms) as a function of frequency in the band 100-915 MHz. Consistent with some of the experimental data in the literature, the highest part-body-averaged specific absorption rate for the head and neck region (as well as for the eyes and brain) occurs at 200 MHz for the isolated condition and at 150 MHz for the grounded condition of the model. Also observed is an increasing specific absorption rate for the eyes for frequencies above 350 MHz due to the superficial nature of power deposition at increasing frequencies.

[Study on schistosomiasis control strategy in Ertan reservoir].

OBJECTIVE: To explore means and strategies of preventing the spread of schistosomasis transmission due to the building of Ertan Dam. METHODS: To eliminate the infection sources and Oncomelania snails. To install concrete irrigation and piping system of water supply. To encourage the immigrants to build methane-generating tanks and improve sanitary facilities and conditions for families who live near the water-retaining line. RESULTS: 2,360 people and 152 cattle were treated for schistosome infection. Mollusciciding and environmental modification were made for eliminating snails at an area of 3,634,580 m2 and 67,105.5 m2 respectively. The length of concrete irrigation and piping system installed was 51.13 and 104.895 km respectively. Methane-generating tanks, water-heating instruments using solar energy and other sanitary facilities were established in 1,781 households. After three-year intervention, no infected snails were found and no infected human being, cattle and wild rats were detected. CONCLUSION: Schistosomiasis control was financially supported since the very beginning of the Ertan Dam project, which provided a condition for sustainable development. Continued surveillance of snails and infection sources should be carried out, which will provide scientific basis for schistosomiasis control in the Three Gorges region as well as other new projects of hydropower and water conservancy in endemic area.

The effect of bile diversion on satiety and fat absorption from liquid and solid dietary sources.

In previous studies, liquid fat has been used to determine the effect of bile diversion on fat absorption. Since protein digests, in addition to bile salts, are capable of solubilizing lipids, we hypothesized that fat incorporated in the protein-rich matrix of solid food would be less sensitive to bile diversion than fat ingested as an oil or liquid. Using [3H]glycerol triether as a nonabsorbable fat recovery marker, we determined how much [14C]triolein was absorbed from solid (chicken liver) and liquid (margarine) dietary sources. After a standard liquid/solid meal with either the chicken liver or margarine labeled, midintestinal chyme was collected for 6 hr, extracted, and counted for 14C and 3H activity. Zero, eighty, or one hundred percent of endogenous bile was diverted. Fat absorption from both chicken liver and margarine was nearly complete by midintestine with 0% diversion and was little affected by diversion of 80% of bile. Complete biliary diversion significantly decreased fat absorption from margarine (87.9 +/- 4.4 to 37.2 +/- 9.2%, P less than 0.05) but reduced [14C]triolein absorption from chicken liver less consistently and insignificantly (78.8 +/- 6.9 to 43.9 +/- 10.6%). These data indicate that fat absorption is not solely dependent on bile and support the hypothesis that fat ingested in a cellular matrix is less dependent on bile than liquid fat. Using these same animals but with the midintestinal cannulas plugged to expose the distal intestine to unabsorbed luminal nutrients, we also demonstrated that bile diversion of an initial meal reduced food consumption at a meal offered 3 hr later.

Preduodenal mechanisms compensate completely for absent pancreatic enzymes to stimulate gallbladder after meals.

We studied gallbladder emptying with gamma scintigraphy in nine dogs prepared with chronic pancreatic fistulas, so that pancreatic enzymes could be either completely excluded from the duodenum or supplied in normal amounts. During duodenal perfusion of the fasted dogs with fat emulsions, gallbladder emptying was significantly less rapid when the emulsion contained inactive vs active enzymes, confirming the potency of lipolytic products in the intestine as stimuli of gallbladder emptying. However, after feeding either a 115-g or a 460-g meal, each 18% fat, the gallbladders emptied identically whether or not pancreatic enzymes were excluded from the duodenum. We concluded that while products of pancreatic lipolysis in the small intestine are potent stimuli of gallbladder contraction, preduodenal mechanisms can compensate completely for the absence of pancreatic hydrolysis in stimulating gallbladder emptying after a meal.

Frequency of gastric pacesetter potential depends on volume and site of distension.

Little is known about the response of the frequency of gastric pacesetter potential (PP) to luminal distension. When volume distension occurs as a result of a meal, gastric emptying may play an important role, since the site of distension shifts as the meal is displaced from the stomach to the small bowel. In this study, using does equipped with duodenal fistulas and serosal electrodes on the antrum, we compared the frequency of gastric PP during the course of gastric emptying while isolating the volume distension to either the stomach or the small bowel. We found that 1) the frequency of gastric PP decreased linearly with greater initial meal volume when volume distension was isolated to either the stomach -P<0.05, analysis of variance (ANOVA)- or small bowel (P<0.01, ANOVA), and 2) the frequency of gastric PP decreased linearly with increased volume remaining in the stomach or increased volume entering the small intestine. We conclude that the frequency of gastric PP depends on the volume and site of distension.

Nutrient feedback inhibition of gastric emptying plays a larger role than osmotically dependent duodenal resistance.

The slowing of gastric emptying by hyperosmolar solutions has been postulated to result from the triggering of duodenal osmoreceptor feedback on the stomach. We tested the idea that the inhibition of gastric emptying by a hyperosmolar solution depended on the duodenal resistance and the triggering of nutrient-specific feedback by tracking gastric emptying of 300 and 1,200 mosmol/kgH2O test solutions in 12 dogs in which duodenal resistance was either removed (by temporarily diverting chyme from uncorked duodenal fistula) or preserved (by keeping duodenal fistula corked). Mannitol was used to test osmolality alone, and glucose was used to examine the combined effects of osmolality and nutrient-specific inhibitory feedback. We found that: 1) the slowing effect of hyperosmolality was more marked with the duodenal resistance preserved (P < 0.05; analysis of variance), 2) the slowing effect of glucose was greater than that of mannitol for all conditions (P = 0.01; analysis of variance), and 3) the inhibitory effect of mannitol was localized to the duodenum. We conclude that inhibition of gastric emptying by hyperosmolar mannitol depended primarily on duodenal resistance, while the inhibitory effect of hyperosmolar glucose depended on nutrient-specific feedback on the stomach more than duodenal resistance.

trans-2,6-,3,6- and 4,6-diaza-5,6,6a,7,8,12b-hexahydro-benzo[c]phenanthrene-10,11- diols as dopamine agonists.

The title compounds were synthesized by replacing the thiophene moiety of A-86929(2a) with variously substituted pyridines. Dopamine D-1 and D-2 binding and adenylate cyclase assays indicate that 4,6-diaza compounds 15 are potent and selective full D1 agonists when R1 is H or a small substituent and R2 = H, with D1 binding affinity and adenylate cyclase functional potency equivalent to that of A-86929(2a).

Disproportionate ileal digestion on canine food consumption. A possible model for satiety in pancreatic insufficiency.

In animals, ileal sensors of nutrients signal satiety more potently than similar sensors in jejunum. We postulated that inadequate food intake and weight loss in human pancreatic insufficiency might arise by the displacement of digestion to ileum, where excessive release of digestive products would enhance satiety. To test this idea, we studied dogs prepared with pancreatic fistulas, which allowed reversible switching of pancreatic juice from entry at duodenum to entry at mid-small intestine. Dogs were studied in a crossover design over successive eight-day periods. Food consumption and body weight were measured while the dogs had continuous access to food. Diversion of pancreatic juice to mid-intestine significantly (P < 0.01) depressed food intake by an average of 28%. Diversion also significantly (P < 0.01) reduced body weight. The findings support the idea that insufficient food intake in human pancreatic insufficiency may result from stimulation of ileal satiety mechanisms.

Erythromycin accelerates solid emptying at the expense of gastric sieving.

Erythromycin accelerates gastric emptying by inducing antral contractions similar to phase III of interdigestive MMC. These powerful contractions are capable of forcing coin-sized indigestibles out of the stomach. In contrast, fed motility is associated with submaximal contractions that fragment (trituration) and propel solids while retaining large (> 0.5 mm) pieces for further size reduction (gastric sieving). In this study, using dogs with duodenal fistulas, we tested the hypothesis that erythromycin-induced acceleration of gastric emptying resulted in the passage of inadequately triturated (> 0.05 mm) chunks of solids into the duodenum. We found that gastric emptying was accelerated by erythromycin (vs 0.15 M NaCl control, P < 0.05). However, the percentage of chyme collected in the > 0.5-mm fraction was much greater (P < 0.01) in the erythromycin-treated experiments (63 +/- 9%) than the controls (7 +/- 1%). Correspondingly, while a fine gruel was passed during controls, under erythromycin infusion, most of the solids were emptied as large chunks virtually unchanged from the swallowed pieces. We conclude that erythromycin accelerates gastric emptying at the expense of gastric sieving.

Gastric emptying of solid food is most potently inhibited by carbohydrate in the canine distal ileum.

Although glucose sensors regulating the gastric emptying of liquid meals are uniformly distributed throughout the canine small intestine, some data suggest that the distal small bowel more potently inhibits gastric emptying of solid foods. The aims of this study were to compare (a) the inhibition of gastric emptying by glucose sensors in the proximal intestine with the feedback from the distal intestine, (b) these effects on the gastric emptying of solids vs. liquids, and (c) the inhibitory effect of unhydrolyzed starch with glucose. In 7 dogs with chronic duodenal fistulas, the second, third, and fourth quarters of small bowel were perfused via chronically implanted transmural catheters. Gastric emptying of either solids or liquids was tracked by gamma camera while gastric output was diverted out the duodenal fistula and the small bowel perfused with test solutions of glucose (0.06-2.0 mol/L), 0.15 mol/L NaCl, or 8.5% soluble starch. It was found that (a) gastric emptying of solids but not liquids was approximately 3 times more potently inhibited by glucose in the fourth quarter vs. the first or second quarter of small bowel, and (b) only hydrolyzed starch inhibited gastric emptying of solids.

Bile salt-dependent inhibition of gallbladder emptying.

Little is known about the inhibitory controls of gallbladder emptying. Since cholestyramine, a binding agent that reduces luminal concentration of bile salt, has been reported to accelerate gallbladder emptying, suggesting that bile salt is inhibitory, we hypothesized that fat-stimulated gallbladder emptying is inhibited by a bile salt-dependent mechanism. To test this idea, we compared gallbladder emptying in 10 dogs equipped with duodenal and jejunal fistulas that allowed for complete diversion of the native bile while varying concentrations of bile salt were perfused into the small intestine. In six dogs, 30 mM oleate and 5, 10, or 20 mM sodium taurocholate was perfused into the whole intestine. Since bile salt availability alters fat absorption, in a separate experiment in seven dogs we also compared gallbladder emptying while 30 mM oleate and 5 mM taurocholate were perfused between fistula and 0, 5, 10, or 20 mM taurocholate were perfused beyond jejunal fistula to separate fat from varying concentrations of bile salt. We found that intestinal taurocholate inhibited fat-stimulated gallbladder emptying in a dose-dependent fashion (P < 0.01; analysis of variance, significant linear dose effect) and that the inhibitory effect of bile salt persisted when 5-20 mM taurocholate was perfused beyond the jejunal fistula (0 vs. average of 5-20 mM taurocholate, P < 0.05, paired t-test). We conclude that fat-stimulated gallbladder emptying is inhibited by a bile salt-dependent inhibitory mechanism.

Stimulation of duodenal motility by hyperosmolar mannitol depends on local osmoreceptor control.

Duodenal motility is stimulated by hyperosmolar solution. Since intestinal distension also stimulates intestinal motility, this increase in the motility response may be due to either stimulation of duodenal local osmoreceptor control or intestinal distension resulting from osmotic equilibration. To test which mechanism is primarily responsible for this osmotically sensitive effect, we compared the number of duodenal spike bursts in five dogs equipped with duodenal fistulas that allowed for the preservation or removal of intestinal distension. The response to 300 vs. 1,200 mosM mannitol was compared under three experimental perfusion methods: 1) distension was preserved both proximal and distal to the fistula (DD); 2) distension proximal to the fistula was removed (rD); and 3) distension both proximal and distal to the fistula was removed (rr). The test solutions had access to either the whole gut (DD and rD) or only the first 10 cm of the duodenum (rr). We found that 1) there were more spike bursts after the hyperosmolar solution (dose effect, P < 0.05, analysis of variance); 2) there was no significant difference between the three experimental methods; and 3) the stimulating effect of hyperosmolar solution depended on the first 10 cm of the duodenum. Thus, since hyperosmolar solution increased duodenal motility regardless of whether intestinal distension was preserved or removed, the stimulating effect of hyperosmolar solution on duodenal motility was primarily the result of a local osmoreceptor control mechanism located in the first 10 cm of the duodenum.

Control of canine gastric emptying of fat by lipolytic products.

Dietary fat is ingested in three forms: 1) in solid food, 2) as aqueous emulsions, and 3) as unemulsified, liquid oil. On the basis of a scant previous literature, we postulated that liquid fat (emulsions or oils) would empty from the stomach at speeds that varied with the amounts ingested but that this dynamic would be modulated by feedback inhibition from lipolytic products. To test these ideas, we used a gamma camera to track gastric emptying of 123I-labeled fat in dogs with chronic pancreatic fistulas by which lipase was excluded from or replenished in the duodenum in varied amounts after dogs were fed 15-, 30-, and 60-g loads of liquid fat given with solid foods or as emulsions. We also tracked concurrent gastric emptying of 113mIn, which marked the solid food phase or the water phase of emulsions. In some studies, we used a potent and specific inhibitor (orlistat) of pancreatic and gastric lipases to assess how lipolytic products modulated emptying of liquid fat. In the absence of pancreatic enzymes, both oils and emulsions emptied initially at high speeds that varied with fat loads, but emptying slowed 20 min after ingestion of emulsions and 60 min after ingestion of unemulsified oil. Studies with orlistat indicated that these changes in rates resulted from liberation of gastric lipolytic products. Emptying of oil emulsions was not altered by duodenal replenishment with pancreatic enzymes, but emptying of unemulsified oil was inhibited in a dose-related fashion, such that maximal inhibition was achieved when pancreatic enzymes were replenished at > or = 40% of normal amounts. Studies with orlistat confirmed that this dose-dependent slowing was due specifically to lipase. Emptying of solid food was much more sensitive to replenishment with enzymes, so that a 10% replenishment maximally inhibited solid emptying.