An in-line digestive cartridge increases enteral fat and vitamin absorption in a porcine model of short bowel syndrome.

BACKGROUND & AIMS: Short bowel syndrome (SBS) occurs after intestinal loss resulting in parenteral nutrition dependence and micronutrient deficiencies, which may lead to life-limiting complications. ALC-078 is a cartridge containing immobilized lipase that connects in-line with enteral feeding sets and digests fats in enteral nutrition (EN). In this study, we evaluate the efficacy of ALC-078 to improve fat and nutrient absorption in a porcine SBS model. METHODS: Fifteen male Yorkshire piglets were assessed. Animals were randomized to no intestinal resection (n = 5), 75% resection (n = 5), or 75% resection + ALC-078 (n = 5). After recovery, animals were treated for 14 days. Piglets received 60% of nutrition from continuous EN and 40% from chow. The degree of fat malabsorption was determined by the coefficient of fat absorption (CFA) following a 72-h stool collection. Body weight, fat-soluble vitamins, and nutritional markers were assessed. RESULTS: Adverse events were similar across the three groups (P = 1.00). ALC-078-treated animals had similar weight gain compared to resected piglets. Resected animals had a lower CFA compared to unresected controls (79.3% vs. 95.2%, P = 0.01) while there was no significant difference in the ALC-078 animals (87.1% vs. 95.2%, P = 0.19). Between Study Days 1 and 15, ALC-078 animals had increased concentrations of vitamin D (12.2 vs. 8.7 ng/mL, P = 0.0006), and vitamin E (4.3 vs. 2.5 mg/L, P = 0.03). These markers did not significantly change in untreated resected animals. CONCLUSION: ALC-078 increases the absorption of fat-soluble vitamins and may improve fat malabsorption. Future studies should determine whether ALC-078 can reduce PN dependence and if these findings translate to human patients with SBS.

Optical biopsy of benign and malignant tissue by time resolved spectroscopy.

Pathological condition of malignant tissue could be analyzed by spectral domain or time domain spectroscopy, the two being the complementary to each other in optical biopsy (OB) of cancer. This paper reports results of time resolved emission spectroscopy (TRS) of 24 excised tissue samples of breast and prostate (normal control = 12; benign = 4; malignant = 8), employing a 390 nm, 100 fs, Ti-Sapphire laser pulses.The fluorescence decay times were measured using streak camera and the resultant data were fitted for single and bi-exponential decays with reliability of 97%. Our results show the distinct difference between normal, benign and malignant tissues mostly due to the emission spectra of Nicotinamide Adenine Dinucleotide (NADH), Flavin Mononucleotide (FAD) and also due to the heterogeneity of micro environments associated with the diseased tissues. In this short report, fit is also shown that TRS of breast tissues are similar to those of prostate tissues.

Inhibition of Barnyardgrass 4-Hydroxyphenylpyruvate Dioxygenase by Sulcotrione.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) was partially purified from barnyardgrass (Echinochloa crus-galli L.) leaves and assayed by high-performance liquid chromatography analysis of product formation or by the capture of released 14CO2. The bleaching herbicide sulcotrione [2-(2-chloro-4-methanesulfonylbenzoyl)-1,3-cyclohexanedione] was shown to be a potent, linear competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase. Kinetic analyses determined that the Km for the substrate, 4-hydroxyphenylpyruvate, was 4.3 [mu]M, and the Ki value was 9.8 nM for sulcotrione.

The effect of route of administration on the cimetidine-theophylline drug interaction.

The effect of route of cimetidine administration on cimetidine-mediated inhibition of theophylline oxidation was examined in healthy individuals. Based on the evidence that cimetidine-mediated inhibition of drug oxidation is competitive and, therefore, dependent on cimetidine concentration in the liver, oral cimetidine was tested to determine whether it would cause greater inhibition of drug oxidation than intravenous (IV) cimetidine. Both oral and IV cimetidine decreased theophylline clearance to the same extent. However, when clearance was corrected for cimetidine AUC, oral cimetidine resulted in a greater inhibition than IV cimetidine. Thus, the potential for increased inhibitory effect of oral cimetidine was balanced by decreased absorption after oral administration. Degree of inhibition (absolute change in theophylline clearance) and percent of inhibition after cimetidine correlated with the basal theophylline clearance. Individuals with higher basal theophylline clearances had greater degree and percent of inhibition than individuals with lower basal theophylline clearances.

Inhibition of Acetyl-CoA Carboxylase Activity by Haloxyfop and Tralkoxydim.

Acetyl-coenzyme A (CoA) carboxylase from maize (Zea mays L.) is inhibited by nanomolar concentrations of both haloxyfop, an aryloxyphenoxypropionate, and tralkoxydim, a cyclohexanedione herbicide. These results suggest that acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid biosynthesis, may be the target of these herbicides, contrary to an earlier report suggesting that aryloxyphenoxypropionate herbicides do not inhibit acetyl-CoA carboxylase.

Regulation of sucrose efflux from soybean leaf discs.

Net sucrose efflux from discs of fully expanded leaves of soybean (Glycine max [L.] Merr.) plants was studied to characterize sucrose efflux into the apoplast. Net sucrose efflux had a Q(10) of 2.3, was linear for at least 3.5 hours, and was selective for sucrose over glucose. Sulfhydryl group inhibitors reduced sucrose efflux by up to 80%. There was a biphasic promotion of sucrose efflux by KCl with an apparent saturable component up to about 20 millimolar, above which the effect was linear. Sucrose efflux was promoted by NaCl as a linear function of concentration. Monovalent cation ionophores did not affect sucrose efflux, regardless of external KCl concentration. Light in the absence of added HCO(3)-increased sucrose efflux by about 20%. Sucrose efflux was promoted by increasing pH from 4 to about 8, above which no additional effect was observed. When leaf discs were bathed at pH 6.0, the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) increased sucrose efflux by about 25%. CCCP in the presence of valinomycin had the same effect as CCCP alone. Inhibition of plasmalemma ATPase activity with N,N'-dicyclohexylcarbodiimide, diethylstilbestrol, or orthovanadate increased sucrose efflux. These data indicate that sucrose efflux from soybean leaf discs is not a result of simple leakage but is a regulated process.

Effects of age and sex on the hepatic monoxygenase system: a correlative approach.

The following studies compare developmental patterns of a hepatic monoxygenase system using (1) the aminopyrine (Ap) breath test, (2) in vivo Ap pharmacokinetics (clearances) and (3) in vitro Ap demethylation by hepatic microsomes. Together, the three methodological approaches indicate that hepatic metabolism of Ap increases from the fetal stage through 70 days of age with the male showing a significantly greater drug metabolizing capacity than the female. However, sex and developmental patterns derived by the three methodologies do not necessarily correlate quantitatively, due to a number of complex variables (i.e., liver size, drug volume of distribution, etc.) less likely encountered in the adult of fixed age and mature sexual development.

Lack of effect of nizatidine on hepatic drug metabolism in man.

The effect of nizatidine, a new H2-receptor antagonist, on the hepatic metabolism of three probe drugs was studied in normal volunteers. The drugs studied were chlordiazepoxide and theophylline which are metabolized in part by N-demethylation by the hepatic microsomal cytochrome P-450 system and lorazepam which is conjugated to lorazepam glucuronide. A 7 day course of nizatidine did not interfere with the disposition of any of these therapeutic agents in man.

Rapid Accumulation of gamma-Aminobutyric Acid and Alanine in Soybean Leaves in Response to an Abrupt Transfer to Lower Temperature, Darkness, or Mechanical Manipulation.

Soybean (Glycine max [L.] Merr) leaves contain a low level (0.05 micromole per gram fresh weight) of gamma-aminobutyric acid (Gaba) but the concentration of this non-protein amino acid increased to 1 to 2 micromoles per gram fresh weight within 5 minutes after transfer of plants or detached leaves from 33 degrees C to 22 degrees C or lower temperatures. A parallel decrease occurred in the concentration of glutamate. Accumulation of Gaba was also triggered by mechanical damage to the soybean leaves, but in plants subjected to a gradual reduction in temperature (2 degrees C per minute) only a small increase in Gaba occurred. A rapid increase in the concentration of alanine and decrease in glycine occurred upon transfer of the soybean plants to darkness and was not influenced by temperature. When plants were returned to normal growing conditions, all changes in amino acid concentrations were fully reversed in 1 hour.In soybean leaf discs incubated with [(14)C]glutamate, a rapid accumulation of [(14)C]Gaba was detected, and glutamate decarboxylase activity of the soybean leaf considerably exceeded (>30-fold) that of Gaba pyruvate transaminase. Part of the transaminase was localized in the mitochondria, but glutamate decarboxylase was not associated with any organelle or membrane component of the leaf cell. We consider that Gaba accumulation results from some change in intracellular compartmentation of the cell triggered by low temperature shock or mechanical damage. The accumulation of alanine due to a light-dark transition could be accounted for by transamination. [(14)C]Alanine formation was demonstrated when soybean leaf extracts were incubated with glutamate, aspartate, or serine and [(14)C]pyruvate.The changes in amino acid concentrations described for soybean leaves were demonstrated for all the vegetative tissues of the soybean plant and at variable rates in the leaves of a range of plant species. The response in detached tomato (Lycopersicon esculentum Mill.) leaves was of a similar magnitude to soybean. Thus, precautions are necessary to minimize changes in amino acid composition induced by manipulation and extraction of plant material.

Characterization of amino Acid efflux from isolated soybean cells.

Cells from reproductive soybean (Glycine max [L.] Merr.) plants were isolated using a mechanical-enzymic technique that produced a high yield of uniform, physiologically active cells. Cells were incubated in a pH 6.0 buffered solution and subjected to various treatments in order to determine the nature of net amino acid efflux. Total net amino acid (ninhydrinreactive substances) efflux was not affected by the following conditions: (a) darkness, (b) aeration, (c) K(+) concentrations of 0.1, 1.0, 10, or 100 millimolar and (d) pH 4, 5, 6, 7, or 8. The Q(10) for net amino acid efflux between 10 degrees C and 30 degrees C was 1.6. Thus, it seems that net amino acid efflux requires neither current photosynthetic energy nor a pH/ion concentration gradient. Amino acid analyses of the intra-and extracellular fractions over time showed that each amino acid was exported linearly for at least 210 minutes, but that export rate was not necessarily related to internal amino acid pools. Amino acids that were exported fastest were alanine, lysine, leucine, and glycine. Addition of the inhibitor p-chloromercuriphenyl sulfonic acid, 3(3,4-dichlorophenyl)-1,1-dimethylurea, or carbonylcyanide p-trifluoromethoxyphenylhydrazone increased the rate of total amino acid efflux but had specific effects on the efflux of certain amino acids. For example, p-chloromercuriphenyl sulfonic acid greatly enhanced efflux of gamma-aminobutyric acid, which is not normally exported rapidly even though a high concentration normally exists within cells. The data suggest that net amino acid efflux is a selective diffusional process. Because net efflux is the result of simultaneous efflux and influx, we propose that efflux is a facilitated diffusion process whereas influx involves energy-dependent carrier proteins.

Mechanisms of decubitus ulcer formation--an hypothesis.

Understanding of the etiology of decubitus ulcer formation is fragmentary and the existing literature contains much experimental data that are inconsistent with the idea that pressure sore formation is due extensively to depriving a tissue region of blood. In fact, there is substantial data that illustrate that tissue can remain viable for very extended lengths of time, up to 13 hours, when subjected to externally applied pressures that collapse the blood microvasculature in a region. Based on these observations and on studies done in this laboratory on lymph propulsion and pressure sore prevention, an hypothesis has been formulated that is consistent with the published data and with clinical observations. The hypothesis states that a major contributing factor to pressure sores is the tissue necrosis that is caused by the accumulation of anaerobic metabolic waste products due to occlusion of the lymph vessels.