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An optimized long-wavelength two-color Quantum Well Infrared Photodetector (QWIP) device structure has been designed. This device structure was grown on a three inch semi-insulating GaAs substrate by molecular beam epitaxy (MBE). This wafer was processed into several 640x486 format monolithically integrated 8-9 and 14-15 micron two color (or dual wavelength) QWIP focal plane arrays (FPAs). These FPAs were then hybridized to 640x486 silicon CMOS readout multiplexers. A thinned (i.e., substrate removed) FPA hybrid was integrated into a liquid helium cooled dewar to perform electrical and optical characterization and to demonstrate simultaneous two-color imagery. The 8-9 micron detectors in the FPA have shown background limited performance (BLIP) at 70 K operating temperature, at 300 K background with f/2 cold stop. The 14-15 micron detectors of the FPA have reached BLIP at 40 K operating temperature at the same background conditions. In this presentation we discuss the performance of this long-wavelength dualband QWIP FPA in quantum efficiency, detectivity, noise equivalent temperature difference (NEAT), uniformity, and operability.

Netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was studied for its effects on kidney function and mechanisms by which it is handled by the kidneys. Measurements of glomerular filtration rate (GFR) and urinalysis in chronic rat studies indicated that the nephrotoxicity of netilmicin was remarkably less than that of gentamicin. Gentamicin caused a dose-related reduction in GFR in association with glucosuria and elevated fractional excretion of K + . By contrast, high doses of netilmicin produced only slight reduction in GFR with increased fractional excretion of K + but without glucosuria. In separate experiments, rats were shown to excrete 71 to 90% of netilmicin or gentamicin in 24 h after daily intramuscular administration of doses of 20 or 40 mg/kg for 4 days. In acute experiments on anesthetized dogs, GFR and renal plasma flow were unaffected at serum levels of 11.0 ± 0.6 μg/ml maintained by constant infusion of netilmicin for 5 h. The renal clearance of netilmicin was significantly correlated with GFR. The urinary output of netilmicin was 80.0 ± 4.2% of the infusion rate and was independent of urine flow over the range of 0.04 to 0.33 ml/kg per min. Preferential accumulation of netilmicin occurred in the renal cortex; the cortex–serum and medulla–serum ratios were 9.9 ± 1.2 and 4.2 ± 0.6, respectively. In addition, the extraction ratio of netilmicin, which was lower than that of inulin, suggested that netilmicin reabsorption occurs in the proximal tubule and results in cortical accumulation. It is concluded that netilmicin, like gentamicin, is excreted by the dog kidney by glomerular filtration plus limited reabsorption. However, the new drug is characterized by low intrinsic nephrotoxicity in rats.

Urinary excretion and tissue accumulation of gentamicin and paraaminohippurate in postischemic rat kidneys. Unilateral renal ischemia was induced in rats by clamping the left renal artery for 20, 60, and 120 min, respectively. One hour after the arterial clamp was removed, renal handling of gentamicin and paraaminohippurate (PAH) was studied over the next 2 hours; the kidneys were removed at the end of the experiments for determination of gentamicin and PAH content. The ischemic damage was evidenced by morphologic and functional changes. The glomerular filtration was decreased in proportion to the severity of ischemic injury. The excretion of gentamicin was highly correlated with GFR in normal and postischemic kidneys. In the cortex, ischemic injury resulted in reduced concentrations of gentamicin but markedly augmented those of PAH. The finding is consistent with the hypothesis that gentamicin is reabsorbed by the epithelial cells through the luminal membrane, whereas PAH enters via the peritubular membrane. In contrast, medullary concentrations of both compounds were similar, with suppression of uptake seen only after 120 min of ischemia. Conclusion. Ischemic damage impairs urinary elimination of gentamicin and the ability of renal parenchyma to retain the drug. Difference in uptake between gentamicin and PAH were unmasked in the postischemic kidneys. Excretion urinaire et accumulation tissulaire de gentamycine et de paraaminohippurate dans les reins de rats apres ischemie. Une ischemie renale unilaterale a ete realisee chez des rats par clam-page de l'artere renale gauche pendant 20, 60, et 120 min. Une heure apres l'ablation du clamp arteriel le comportement renal de la gentamycine et du paraaminohippurate (PAH) a ete etudie sur une periode de 2 heures. Au terme de l'experience les reins ont ete preleves pour la determination des contenus en gentamycine et PAH. Les modifications ischemiques ont ete prouvees par les alterations morphologiques et fonctionnelles. La filtration glomerulaire est diminuee en proportion de la severite de l'ischemie. L'excretion de gentamycine est tres correlee au debit de filtration glomerulaire dans les reins normaux et postischemiques. Dans le cortex l'ischemie a pour consequence des concentrations abaissees de gentamycine mais tres augmentees de PAH. Cette constatation est en accord avec l'hypothese selon laquelle la gentamycine est reabsorbee par les cellules epitheliales a travers la membrane luminale alors que le PAH penetre par la membrane peritubulaire. Les concentrations medullaires des deux composes, au contraire, sont semblables et la suppression de la captation n'est observee qu'apres 120 min d'ischemie. Conclusion. L'ischemie altere l'elimination urinaire de gentamycine et la capacite du parenchyme renal de fixer la drogue. Une difference des captations de gentamycine et de PAH apparait dans les reins post-ischemiques.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

The purpose of the present study was to investigate the effect of prednisolone on gastric injury induced by ethanol in the rat. Gastric damage was produced by oral administration of 1 ml of absolute ethanol to rats previously fasted for 24 hr and deprived of water for 19 hr. The severity of the ethanol-induced gastric damage varied considerably within the vehicle-treated group of rats which served as controls. Prednisolone, administered orally as a single dose 15 min before alcohol challenge, significantly decreased the number of rats which developed severe lesions. Prednisolone was effective in increasing the resistance of the gastric mucosa to ethanol when given from 1 to 60 min before alcohol. The steroid proved ineffective when 90 min elapsed between prednisolone and ethanol administration, or when the steroid was given at the same time (0 min) as alcohol. The dose-response curve for prednisolone plateaued at high doses. Our results suggest that a prostaglandin-mediated endogenous cytoprotective potential exists in the rat gastric mucosa. Prednisolone may enhance the degree of mucosal protection afforded by this mechanism.

The present study was designed to determine the effectiveness of medium-chain triglycerides (MCT) as inhibitors of gastric secretion. Varying amounts of MCT, olive oil, or saline were injected into the upper duodenum of rats at the time of pyloric ligation. Gastric inhibition was observed following administration of both MCT and olive oil. The magnitude of the inhibition was directly related to the amount of triglyceride injected. MCT and olive oil productd a similar degree of inhibition for equivalent moles of triglyceride administered. In experiments performed on dogs that had vagally innervated pouches and had been fed a meat meal for gastric stimulation, MCT and olive oil at 1 ml/kg produced significant inhibition of gastric acid output. Following the period of inhibition, a marked rebound of acid output occurred with olive oil but not with MCT.

Publisher Summary This chapter reviews the newer therapeutic agents useful in the treatment of ulcer disease. The major direction being pursued in developing new antiulcer drugs involves effective inhibition of gastric acid secretion as exemplified by the H 2 -receptor antagonists. The unprecedented success of cimetidine as a therapeutic agent has provided the impetus for the development of second generation H 2 -receptor antagonists having greater potency and specificity. In patients with duodenal ulcers, Ranitidine effectively healed the ulcers when administered in 100 mg doses twice daily, and generally was five times as potent as Cimetidine. Metabolically, Ranitidine undergoes N-oxidation and N-demethylation of the 3° amino group and sulfoxide formation. The mechanism, by which prostaglandins (PGs) exert their antiulcer effects, may involve both the inhibitions of gastric acid secretion and/or cytoprotection. All PGs are cytoprotective to varying degrees, but there is no direct relation between cytoprotective and antisecretory effects. The cytoprotective mechanism has not been defined, but may include stimulation of mucus secretion. A comparative study of the effects of Cimetidine, Atropine, and Trimipramine on histamine-stimulated gastric acid secretion in normal subjects confirmed a substantial antisecretory effect for Atropine and Cimetidine, and demonstrated an acid-stimulating property for Trimipramine.

The effect of furosemide on gentamicin excretion and tissue accumulation was studied with clearance techniques in anesthetized rats, at two different infusion rates of saline or Ringer solution. Gentamicin (∼20 mg/kg) was administered by constant intravenous infusion over a period of 3 h. With the low fluid infusion rate, furosemide (25 mg/kg intravenously) caused severe reduction in glomerular filtration rate and diminished urinary output of gentamicin. Serum and renal tissue levels of the antibiotic were significantly elevated. High fluid infusion prevented the decline of the glomerular filtration rate, with near normalization of all measurements. A fluid deficit incurred by furosemide was noted at both the low and high infusion rates. Complete correction of this fluid deficit by continuous adjustment of the infusion rate fully restored normal renal handling of gentamicin. These results suggest that furosemide had no direct effect on renal excretion of gentamicin. In comparison, renal handling of gentamicin in rats did not respond to changes in the rate of fluid infusion in the absence of furosemide therapy. It appears that gentamicin excretion and gentamicin accumulation in the renal cortex in furosemide-treated rats, in contrast with those in untreated rats, are influenced significantly by the rate of fluid infusion. Fluid administration sufficient to maintain the glomerular filtration rate was found to be necessary for appropriate gentamicin elimination, with consequent reduction in serum and renal tissue levels of the drug.

The Armament Altitude Simulation Facility at the Armament Development and Test Center has been adapted for AFATL experiments and tests to measure infrared radiation properties of target simulator plumes. This document briefly describes the facility and associated instrumentation. It supersedes AFATL-TR- 74-15.

A series of 9-[(aminoalkyl)thio]-9H-xanthenes (3-6) and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines (7-10) possessing gastric antisecretory activity in the rat and dog is described Many of the compounds possessed good activity in the pylorus-ligated rat and several inhibited histamine-stimulated gastric acid secretion in the dog. The mechanism of acid secretion inhibition is not related to anticholinergic or histamine (H2) receptor antagonism.

Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.

The application of multiaperture optics systems for pattern recognition is discussed. Multiaperture optics systems inherently perform some degree of optical preprocessing which reduces the amount of information offered to the system to a manageable level and so simplifies pattern recognition. The architecture of a typical multiaperture optics system is described and the performance of the system is computed. Due to the large number of lenses, a special detector array is required. Each detector terminates into a memory location which can be randomly accessed. The architecture of the multiaperture system requires special algorithms for pattern recognition. The basic idea is to treat each eyelet as a binary digit. It is shown that only one number is required to describe a given shape. Recognition is accomplished by looking up the stored recognition number.

The tubular handling of gentamicin (G) and its intrarenal distribution were determined to elucidate the mechanism of G accumulation in the kidney. At a serum level of 11.1 ± 0.5 μg/ml (10 animals), as maintained by constant infusion for 5 h, serum Na + and K + , arterial pressure, effective renal plasma flow and glomerular filtration rate remained undisturbed. The clearance values in milliliters per minute for G, inulin, and p -aminohippuric acid were 40.3 ± 1.8, 49.9 ± 2.8, and 132 ± 14, respectively. The ratio of clearance of G to clearance of inulin was 0.82 ± 0.04 ( P < 0.005), suggesting net reabsorption of G by the renal tubules. The renal cortex/serum ratio for G was 11.9 ± 2.1, and the medulla/serum ratio was 2.7 ± 0.4, indicating greater uptake of G by the cortex. The extraction ratio of p -aminohippuric acid was 0.74 ± 0.03. In contrast, the extraction ratio of G was 0.20 ± 0.03, which was significantly lower than that of inulin (0.30 ± 0.04). It is concluded that the accumulation of G in the cortex was due to tubular reabsorption. Probably some of the reabsorbed G became trapped in the epithelial cells after crossing the luminal membrane, whereas some returned to the circulation.

Most optical instruments in use are modeled after the human eye. The design of insect eyes is fundamentally different and is governed by the laws of multiaperture optics. It can be shown that for certain applications, instruments using multiaperture optics are superior to single aperture instruments. For study of multiaperture optics and function of the insect eye a mechanical model resembling an insect eye was constructed. An individual eyelet of the mechanical model consists of a lens system and a detection system. The diameter of the front lens is 2mm (7mm fl), the aperture of the back lens is lmm (2mm fl). Each eyelet has seven optical fibers which transport the incident light to individual detectors. The model has a total of 100 eyelets (700 detectors). Each detector is sequentially read by a multiplexer which is interfaced with a micro computer, which displays the output on a video terminal.© (1983) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A series of 9-[(aminoalkyl)thio]-9H-xanthenes (3-6) and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines (7-10) possessing gastric antisecretory activity in the rat and dog is described Many of the compounds possessed good activity in the pylorus-ligated rat and several inhibited histamine-stimulated gastric acid secretion in the dog. The mechanism of acid secretion inhibition is not related to anticholinergic or histamine (H2) receptor antagonism.

Gastric secretion stimulated by a 100-g meat meal was inhibited by oleic acid and triolein and the inhibition correlated with absorption of the respective lipids in dogs with vagally innervated gastric pouches. Twenty-six milliliters of lipid were infused into the duodenum at 0.76 ml/min through a duodenal fistula starting 5 min before feeding. Gastric secretion was collected every 30 min and analyzed for acid and pepsin concentrations. Paraffin oil infused at the same rate gave results similar to feeding alone. Lipid absorption was determined by measuring venous plasma radioactivity at 1, 2, 3, 4, and 6 hr after feeding and infusing of C14-labeled oleic acid or triolein. Lipid in intestinal content for 3 hr after feeding was determined in acute experiments. The duration of gastric inhibition was longer and the absorption was slower with oleic acid than with triolein.

The present study was designed to determine the effectiveness of medium chain triglycerides (MCT) as inhibitors of gastric secretion in rats after the diversion of bile into the descending colon. One-half of the experimental animals had biliary flow diverted to the descending colon, while the other one-half received sham operations. Twenty-four hours later, either 1 ml of saline, olive oil, or medium chain triglycerides was injected directly into the upper duodenum at the time of pyloric ligation. The administration of olive oil resulted in a significant inhibition of gastric volume, acid and pepsin secretion in the sham-operated animals, but not in animals with biliary diversion. The administration of medium chain triglycerides resulted in a significant inhibition of gastric volume and acid output in both, the sham operated and biliary-diverted rats. Since bile diversion does not affect the rate of absorption of MCT but does reduce the rate of absorption of olive oil, these results support the concept of a relationship between digestion and/or absorption of fat with the inhibition of gastric secretion.

The amounts of acid and of pepsin secreted by the stomach in response to a meal and to two dose levels of histamine and insulin have been compared in eight dogs with vagally-innervated pouches. The greatest acid output occurred after a ‘maximal’ dose of histamine, while the output after a meat meal usually exceeded that after either dose level of insulin. Feeding was better simulated, in the secretion it evoked, by 0·45 µg./kg./min. of histamine than by any other stimulus used. Large doses of histamine appeared to inhibit pepsin secretion in comparison with a submaximal dose. Both doses of insulin stimulated pepsin secretion to a greater degree than did feeding.