Fractional Rate Constants Research Articles

Effect of climate on the in vitro first-order ruminal disappearance kinetics of dry matter in grain of semi-arid native barley cultivars

An experiment was conducted to determine the in vitro first-order disappearance kinetics of dry matter in grain of six semi-arid native barley cultivars (Hordeum vulgare) adapted to grow at different climates known as cold (Bahman, Makoeei), moderate (Reyhan 03, Kavir) and hot (Dasht and Sahra). Samples (n=10) were assessed for bulk density (BD) and chemical composition. In addition, in vitro first-order kinetics of dry matter disappearance, medium pH and NH3-N concentration were determined using fermentation culture. Data were fitted to an exponential equation model: D(t) = D(i).exp (-k. time) + I; where D(t) was potentially a digestible residues at time t, D(i) was a potentially digestible fraction, k is a fractional rate constant of digestion (h -1 ) and I was an indigestible fraction. Results showed there was significant effect of adaption of varieties to climate on bulk density and crude protein, ash, NDF (neutral detergent fiber), ADF (acid detergent fiber), soluble sugars and starch concentrations in grain of the barley cultivars evaluated (P < 0.01). Barley grain cultivars from cold climate had the highest concentration of NDF and starch, whilst hot climate cultivars showed the highest amount of BD and CP (crude fiber). The amount of ash, ADF and soluble sugar in moderate climate barley grain cultivars was higher than those of the other climates. In vitro first order disappearance of dry matter was significantly (P < 0.01) influenced by the climate. Digestible fraction, fractional rate constant of digestion and indigestible fraction of grain from cold (0.78, 0.15, 0.146), moderate (0.77, 0.16, 0.157) and hot (0.75, 0.19, 0.206) were not similar in pattern. Dasht and Bahman grains had the highest and the lowest fractional rate constant (0.23 and 0.12 h -1 , respectively). Barley grain cultivars from cold and hot climates had the largest digestible fraction and fractional rate constant of digestion, respectively. The relationship between NDF content (g/kg DM) and fractional rate constant of digestion (X) was negative: NDF = 520.9X + 334.2, R 2 = 0.723. It was concluded that ruminal dry matter disappearance kinetic differences

The Effect of Heat or Heat-Xylose Processing on Nitrogen Fractions and &lt;I&gt;in Situ&lt;/I&gt;/&lt;i&gt;In Vitro&lt;/i&gt; Ruminal and Post-Ruminal Protein Disappearance of Guar Meal

Problem statement: Guar meal is a by-product consisting of hull and germ and is mostly used as a protein source in poultry and ruminant rations. The aim was to determine the effect of heat or heat-xylose processing on nitrogen fractions, in situ ruminal degradation parameters and in situ/in vitro ruminal and post-ruminal disappearance of guar meal. Approach: Samples were intact Guar Meal (GM), heat processed GM (GMhp, GM was heated at 100°C for 45 minute using industrial heater) and heat-xylose processed GM (GMhx, xylose was included in GM to give a final concentration of 10 g kg−1 DM, then was heat processed at 100°C for 45 minute using industrial heater). Ruminal degradation parameters of DM and Crude Protein (CP) were determined by in situ technique using four ruminally fistulated sheep. Post-ruminal disappearance of ruminal-undegradable CP was determined on residue from 16 h ruminal incubation of guar meal samples by three-step in situ/in vitro enzymatic procedure. Results: Non-protein nitrogen of the GMhx and GM samples ranged from 218-319 (g kg−1 N). Acid detergents insoluble nitrogen concentration of both GM and GMhp was significantly lower than that of GMhx (10.3, 11.29 and 18.53 g kg−1 nitrogen, respectively). In situ fractional degradation rate constant (c) of DM and CP was significantly decreased as a result of heat-xylose processing. Effective crude protein degradability of GMhp and GMhx was higher than that of GM. Post-ruminal disappearance of ruminal-undegradable CP of GM hx (0.965) was significantly higher compared with GM and GMhp (0.918 and 0.906, respectively). Conclusion: Results of the present study demonstrated that heat and heat-xylose processing might effectively protect the DM and CP of guar meal from ruminal degradation.

Effect of a high cornstarch diet on hepatic cytochrome P450 2C and 3A activity and progesterone half-life in dairy cows

In the cow, inadequate concentrations of progesterone during gestation may lead to an abrupt termination of pregnancy. The primary organ involved in progesterone catabolism is the liver, which contains an abundance of cytochrome P450 isozymes (EC 1.14.14.1; mixed-function monooxygenases). The objectives of the current experiment were to determine the effect of feeding 2 isoenergetic and isonitrogenous diets, formulated to cause divergent insulin secretion, on hepatic cytochrome P450 2C (CYP2C) and 3A (CYP3A) activity as well as the resulting biological half-life of progesterone. Twenty-two Holstein cows averaging 80±7 d in milk were randomly assigned to either a high cornstarch diet or a high fiber diet in a crossover experimental design consisting of two 14-d periods. Dry matter intake, milk yield, milk lactose yield, and milk lactose percentage were similar between the 2 diets. Milk fat yield and milk fat percentage were higher in cows fed the high fiber diet, whereas milk protein yield tended to be higher and milk protein percentage was higher in cows fed the high cornstarch diet. Energy balance tended to be improved by 57% in cows consuming the high cornstarch diet. Insulin concentrations at the time of liver biopsy (3.16±0.04h post-feeding) were increased by 44% in cows consuming the high cornstarch diet compared with cows consuming the high fiber diet. Cytochrome P450 2C activity was decreased by 45%, whereas CYP3A activity tended to be lowered by 34% in cows consuming the high cornstarch diet. Cytochrome P450 2C mRNA expression tended to be decreased by 21% in cows fed the high cornstarch diet, whereas CYP3A mRNA expression was not different between the dietary treatments. The fractional rate constant of progesterone decay was not different between the 2 diets; however, the half-life of progesterone tended to be longer in cows fed the high cornstarch diet compared with cows fed the high fiber diet (85 vs. 64min, respectively). In summary, cows consuming the high cornstarch diet had increased insulin concentrations and lower hepatic CYP2C and CYP3A activity and tended to have a longer progesterone half-life compared with cows consuming the high fiber diet. Feeding diets that stimulate insulin secretion could alter progesterone clearance during lactation, when dairy cows have increased rates of progesterone inactivation because of high energy demands and increased DMI.

Degradation Kinetics of Carbohydrate Fractions of Ruminant Feeds Using Automated Gas Production Technique

The current ruminant feeding models require parameterization of the digestion kinetics of carbohydrate fractions in feed ingredients to estimate the supply of nutrients from a ration. Using an automated gas production technique, statistically welldefined digestion rate of carbohydrate, including soluble carbohydrate, can be estimated in a relatively easy way. In this study, the gas production during in vitro fermentation was measured and recorded by an automated gas production system to investigate degradation kinetics of carbohydrate fractions of a wide range of ruminant feeds: corn silage, rice straw, corn, soybean hull, soybean meal, and cell mass from lysine production (CMLP). The gas production from un-fractionated, ethanol insoluble residue and neutral detergent insoluble residue of the feed samples were obtained. The gas profiles of carbohydrate fractions on the basis of the carbohydrate scheme of the Cornell Net Carbohydrate and Protein System (A, B1, B2, B3 and C) were generated using a subtraction approach. After the gas profiles were plotted with time, a curve was fitted with a single-pool exponential equation with a discrete lag to obtain kinetic parameters that can be used as inputs for modern nutritional models. The fractional degradation rate constants (Kd) of corn silage were 11.6, 25.7, 14.8 and 0.8%/h for un-fractioned, A, B1 and B2 fractions, respectively. The values were statistically well estimated, assessed by high t-value (>12.9). The Kd of carbohydrate fractions in rice straw were 4.8, 21.1, 5.7 and 0.5%/h for un-fractioned, A, B1 and B2 fractions, respectively. Although the Kd of B2 fraction was poorly defined with a t-value of 4.4, the Kd of the other fractions showed tvalues higher than 21.9. The un-fractioned corn showed the highest Kd (18.2%/h) among the feeds tested, and the Kd of A plus B1 fraction was 18.7%/h. Soybean hull had a Kd of 6.0, 29.0, 3.8 and 13.8%/h for un-fractioned, A, B1 and B2, respectively. The large Kd of fraction B2 indicated that NDF in soybean hull was easily degradable. The t-values were higher than 20 except for the B1 fraction (5.7). The estimated Kd of soybean meal was 9.6, 24.3, 5.0%/h for un-fractioned, A and B1 fractions, respectively. A small amount of gas (5.6 ml at 48 ho of incubation) was produced from fermentation of CMLP which contained little carbohydrate. In summary, the automated gas production system was satisfactory for the estimation of well defined (t-value >12) kinetic parameters and Kd of soluble carbohydrate fractions of various feedstuffs that supply mainly carbohydrate. The subtraction approach, however, should be applied with caution for some concentrates, especially those which contain a high level of crude protein since nitrogen-containing compounds can interfere with gas production.

Behavior of inactivation kinetics of Escherichia coli by dense phase carbon dioxide

Inactivation of Escherichia coli in cloudy apple juice by dense phase carbon dioxide (DPCD) was investigated. The pressures were 10, 20 and 30 MPa, the temperatures were 32, 37 and 42 °C. The inactivation kinetic behavior of E. coli conformed to a sigmoid curve with a shoulder and a tail, which was closely related with temperature or pressure. With the increase of temperature or pressure, the shoulder became unclear or even disappeared. The experimental data were well fitted to a model proposed by Xiong et al. [Xiong, R., Xie, G., Edmondson, A.E., Sheard, M.A., 1999. A mathematical model for bacterial inactivation. International Journal of Food Microbiology 46, 45–55], the kinetic parameters of t lag (the lag time length), f (the initial proportion of less resistant population), k 1 (the inactivation rate constant of less resistant fraction) and k 2 (the inactivation rate constant of resistant fraction), and t 4 − D (the time required for an 4-log-cycle reduction of bacteria under a given condition) were obtained from this model. The t lag declined from 4.032 to 0.890 min and t 4 − D from 54.955 to 18.840 min, k 1 was 1.74–4.4 times of k 2. Moreover, the model was validated by more experimental data, the accuracy factor ( Af), bias factor ( Bf), root mean square error (RMSE), sum of squares (SS), and correlation coefficient ( R 2) were used to evaluate this model performance, indicating that the model could provide a good fitting to the experimental data.

Short Communication: Insulin Alters Hepatic Progesterone Catabolic Enzymes Cytochrome P450 2C and 3A in Dairy Cows

High proportions of embryonic and early fetal losses in dairy cattle are associated with low peripheral concentrations of progesterone, which could result from increased catabolism, decreased production, or both. Progesterone catabolism occurs primarily in the liver via the cytochrome P450 2C (CYP2C) and cytochrome P450 3A (CYP3A) subfamilies (EC 1.14.14.1; unspecific monooxygenases). Recent observations from our laboratory have shown that the fractional rate constant of progesterone decay can be dramatically reduced by insulin because of a decrease in hepatic CYP2C and CYP3A activity. Little information exists on the regulation of progesterone catabolic enzymes in dairy cows. We hypothesized that elevated insulin concentrations would down-regulate hepatic CYP2C and CYP3A mRNA; therefore, our objectives were to determine the relative abundance of hepatic CYP2C and CYP3A mRNA in dairy cows in response to elevated concentrations of insulin. In the first experiment, 17 mature Holstein cows were drenched daily with 500mL of water (n=10) or propylene glycol (a gluconeogenic substrate; n=7) from 10 d before their expected calving date until d 25 postpartum. Cows drenched with propylene glycol had a 30% increase in peripheral concentrations of insulin. Liver biopsies were collected on d 25 postpartum to determine the relative abundance of CYP2C and CYP3A mRNA. In the second experiment, 19 mature, lactating Holstein cows were randomly assigned to a hyperinsulinemic-euglycemic clamp (0.3 or 1.0μg of insulin/kg of BW per h; n=6 each) or remained as controls (saline infused; n=7) for 96h beginning on d 10 postpartum. Insulin infusion resulted in a 2.6- or 8- fold increase in peripheral concentrations of insulin, respectively. On d 14 postpartum, a liver biopsy was collected to determine CYP2C and CYP3A mRNA abundance. In experiment 1, the relative abundance of CYP2C mRNA in cows treated with propylene glycol did not differ from controls; however, the relative abundance of CYP3A mRNA in the propylene glycol group was 63% that of controls. For experiment 2, there was a dose-dependent decrease in the relative abundance of both CYP2C and CYP3A mRNA with increasing dosage of insulin. In conclusion, this study demonstrated that, in the cow, either providing a gluconeogenic feed-stuff or treatment with insulin decreased the abundance of mRNA for enzymes responsible for hepatic progesterone catabolism.

Three thiamine analogues differently alter thiamine transport and metabolism in nervous tissue: an in vivo kinetic study using rats.

Thiamine (T) analogues pyrithiamine, oxythiamine or amprolium in amounts 10-1000 times higher than labelled T, were i.p. injected into rats together with 14C-T (30 microg; 46.25 KBq). The radioactivity associated with T and its phosphoesters in the plasma and cerebral cortex, brainstem, cerebellum, and sciatic nerve were determined at time intervals from 0.25 to 240 h from injection. The experimental data obtained were processed with a mathematical compartmental model that calculated the fractional rate constants. These are the amount of content in a given compartment that is replaced in 1 h and expressed in per hour. The results showed that all three analogues inhibited thiamine entry from plasma. Instead, oxythiamine enhanced T phosphorylation to T pyrophosphate (TPP); amprolium and oxythiamine enhanced TPP dephosphorylation to monophosphate (TMP); pyrithiamine reduced TPP dephosphorylation and TMP formation, while none of the analogues modified TMP dephosphorylation to T. In conclusion, in living rats, the action of T analogues was much more complex than could be expected from their structure and action in vitro.

Decomposition and plant-available nitrogen in biosolids: laboratory studies, field studies, and computer simulation.

This research combines laboratory and field studies with computer simulation to characterize the amount of plant-available nitrogen (PAN) released when municipal biosolids are land-applied to agronomic crops. In the laboratory studies, biosolids were incubated in or on soil from the land application sites. Mean biosolids total C, organic N, and C to N ratio were 292 g kg(-1), 41.7 g kg(-1), and 7.5, respectively. Based on CO2 evolution at 25 degrees C and optimum soil moisture, 27 of the 37 biosolids-soil combinations had two decomposition phases. The mean rapid and slow fraction rate constants were 0.021 and 0.0015 d(-1), respectively, and the rapid fraction contained 23% of the total C assuming sequential decomposition. Where only one decomposition phase existed, the mean first order rate constant was 0.0046 d(-1). The mean rate constant for biosolids stored in lagoons for an extended time was 0.00097 d(-1). The only treatment process that was related to biosolids treatment was stabilization by storage in a lagoon. Biosolids addition rates (dry basis) ranged from 1.3 to 33.8 Mg ha(-1) with a mean value of 10.6 Mg ha(-1). A relationship between fertilizer N rate and crop response was used to estimate observed PAN at each site. Mean observed PAN during the growing season was 18.9 kg N Mg(-1) or 37% of the biosolids total N. Observed PAN was linearly related to biosolids total N. Predicted PAN using the computer model Decomposition, actual growing-season weather, actual analytical data, and laboratory decomposition kinetics compared well with observed PAN. The mean computer model prediction of growing-season PAN was 19.2 kg N Mg(-1) and the slope of the regression between predicted and observed PAN was not significantly different from unity. Predicted PAN obtained using mean decomposition kinetics was related to predicted PAN using actual decomposition kinetics suggesting that mean rate constants, actual weather, and actual analytical data could be used in estimation of PAN. There was a linear relationship between predicted N mineralization for the growing season and for the first year. For this study, the mean values for the growing season and year were 27 and 37% of the organic N, respectively.

Rumen Degradation and Availability of Various Amounts of Liquid Methionine Hydroxy Analog in Lactating Dairy Cows

Ruminal escape of various amounts of methionine hydroxy analog [D,L-2-hydroxy-4-(methylthio)-butanoic acid (HMB)] was measured in an experiment designed as a 4×4 Latin square using four lactating dairy cows with cannula in the rumen and duodenum. The cows were fed a diet composed of corn silage, alfalfa haylage, rolled barley grain, canola meal, and blood meal, three times per day. The cows were fed the liquid analog each day for 1 wk before the experiment was started. On the day of the experiment, each cow received an intraruminal bolus dose of 0, 25, or 50g of the liquid analog (Alimet feed supplement, 88% HMB) or 51.2g of a dry calcium salt of the analog (86% HMB; MHA) mixed with 0.5kg of ground barley grain. A liquid phase marker (Co-EDTA) was administered as a bolus dose into the rumen at the time of administration of the methionine hydroxy analogs. Rumen and duodenal contents, and blood serum were collected at 0, 1, 3, 6, 9, 12, and 24h relative to the time of dosing. Rumen and duodenal samples were analyzed for Co and HMB, and serum was analyzed for free methionine. Fractional rate constants for the passage of the liquid marker (kp) and the decline of HMB concentration in the rumen (krHMB) were determined by nonlinear regression. Liquid passage from the rumen was similar among the four analog treatments (0.136±0.012 /h; X¯ ±SEM). Ruminal escape of HMB as a percentage of the dose (100% x kp/krHMB) did not differ between cows receiving 25, 50, and 51.2g of the methionine analogs (42.5, 41.0, and 34.9±9.0%, respectively) and averaged 39.5%. Duodenal appearance of HMB as a percentage also did not differ between cows receiving 25, 50, and 51.2g of the methionine analogs (16.2, 26.8, and 22.7%, respectively) and averaged 22%. Omasal absorption of HMB was variable ranging from 12.3 to 26.3% and averaged 17.6%. Serum methionine concentration peaked at 3 and 6h after dosing and increased in proportion to the amount of the analog administered. It was concluded that 39.5% of the methionine hydroxy analog escaped rumen degradation, the percentage of the dose that escaped the rumen was not affected by the amount or form of the methionine analog fed, and the analog that escaped ruminal degradation was likely absorbed and metabolized to methionine.

Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation.

Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively modulates the action of GABA at these receptors. Unlike ALLO, 5alpha-dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular progesterone receptors that regulate DNA transcription. To investigate the physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted a mouse model involving protracted social isolation. In the frontal cortex of mice, socially isolated for 6 weeks, both neurosteroids were decreased by approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of the enzyme (5alpha-reductase Type I and II) that converts progesterone into 5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group-housed and socially isolated mice decreased exponentially to 10%-20% of control values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and 5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any given steady-state estimate the rate of synthesis required to maintain that steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis rates were decreased to 30% of the values calculated in group-housed mice. Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I mRNA and protein was approximately 50% lower than in group-housed mice whereas 3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups. Protracted social isolation in mice may provide a model to investigate whether 5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonists, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABA(A) receptors.

Neurotoxicity after hypoxia/during ischemia due to glutamate with/without free radicals as revealed by dynamic changes in glucose metabolism

Fresh rat brain slices were incubated with [ 18F]2-fluoro-2-deoxy- d-glucose ([ 18F]FDG) in oxygenated Krebs–Ringer solution at 36°C, and serial two-dimensional time-resolved images of [ 18F]FDG uptake in the slices were obtained on imaging plates. The fractional rate constant of [ 18F]FDG (proportional to the cerebral glucose metabolic rate) from pre-loading of ischemia (O 2 and glucose deprivation)/hypoxia (O 2 deprivation) to the reperfused/reoxygenated post-loading phase was quantitatively evaluated by applying the Gjedde–Patlak graphical method to the image data. Against ischemia an N-methyl- d-aspartate antagonist and hypothermia, but not a free radical scavenger, showed a protective effect when administered during ischemia, whereas no such effect was achieved with any of the above agents when administered after reperfusion. Against hypoxia, there was no protective effect with any of the above agents when administered during hypoxia, although an effect was noted with each when administered after reoxygenation. Excitatory amino acids during ischemia loading were found to be the main factor in the neuronal damage associated with ischemia, while in hypoxia, excitatory amino acids working in tandem with free radicals immediately after reoxygenation were implicated.

Inactivation of orange pectinesterase by combined high-pressure and -temperature treatments: a kinetic study.

Pressure and/or temperature inactivation of orange pectinesterase (PE) was investigated. Thermal inactivation showed a biphasic behavior, indicating the presence of labile and stable fractions of the enzyme. In a first part, the inactivation of the labile fraction was studied in detail. The combined pressure-temperature inactivation of the labile fraction was studied in the pressure range 0.1-900 MPa combined with temperatures from 15 to 65 degrees C. Inactivation in the pressure-temperature domain specified could be accurately described by a first-order fractional conversion model, estimating the inactivation rate constant of the labile fraction and the remaining activity of the stable fraction. Pressure and temperature dependence of the inactivation rate constants of the labile fraction was quantified using the Eyring and Arrhenius relations, respectively. By replacing in the latter equation the pressure-dependent parameters (E(a), k(ref)(T)()) by mathematical expressions, a global model was formulated. This mathematical model could accurately predict the inactivation rate constant of the labile fraction of orange PE as a function of pressure and temperature. In a second part, the stable fraction was studied in more detail. The stable fraction inactivated at temperatures exceeding 75 degrees C. Acidification (pH 3.7) enhanced thermal inactivation of the stable fraction, whereas addition of Ca(2+) ions (1 M) suppressed inactivation. At elevated pressure (up to 900 MPa), an antagonistic effect of pressure and temperature on the inactivation of the stable fraction was observed. The antagonistic effect was more pronounced in the presence of a 1 M CaCl(2) solution as compared to the inactivation in water, whereas it was less pronounced for the inactivation in acid medium.

Ruminal escape, gastrointestinal absorption, and response of serum methionine to supplementation of liquid methionine hydroxy analog in dairy cows.

Availability of liquid methionine hydroxy analog [D,L-2-hydroxy-4-(methylthio)-butanoic acid] was evaluated in two experiments using four cannulated lactating dairy cows. The first experiment was designed as a 4 x 4 Latin square. Each cow received a pulse dose of 0, 30, 60, or 90 g of the methionine analog in the rumen each day for 10 d. Duodenal samples were collected at 16, 20, and 24 h after dosing for the last 5 d and pooled. The methionine analog was not detected in duodenal contents because it passed rapidly from the rumen relative to the sampling protocol. In the second experiment, cows were offered 90 g of the methionine analog and 600 ml of Cr-EDTA (3.5 g of Cr) mixed with ground corn for a period of 20 min after which any remains of the treatment were placed in the rumen. The concentration of the analog peaked in ruminal and duodenal fluid at 1 and 3 h, respectively. Based on the fractional rate constants for ruminal and duodenal disappearance of the methionine analog and passage of the liquid, it was determined that 50.0 +/- 2.8% of the methionine analog escaped ruminal degradation and became available for intestinal absorption (44.6 +/- 5.7%) or was absorbed from the omasum (5.4 +/- 3.3%). Serum methionine concentration peaked 6 h after analog dosing at a level that was three times the predose level, indicating that the methionine analog that escaped ruminal degradation was absorbed and metabolized to methionine.

The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL)

We hypothesized that changes in the pharmacokinetics of lidocaine might reveal changes in portal circulation induced by catecholamines. Isolated perfused rat liver (IPRL) was selected as an experimental model, since experimental conditions in this model could be regulated. The liver was perfused with a recirculating system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was administered along with one of three drugs, dopamine, norepinephrine or adenosine triphosphate. The fractional transfer rate constants, k 21 and k 12, from medium to liver and liver to medium, respectively, and k e, the elimination rate constant, were calculated using a two-compartment model with the SAAM II TM program. Curves of decay of lidocaine from the recirculating medium consisted of a fast and a slow component. Norepinephrine and high-dose dopamine significantly increased k 12, while low-dose dopamine significantly increased k 21 and k e compared with control values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer rate from liver to medium, while low-dose dopamine increased the transfer rate from medium to liver and the rate of elimination from liver. These findings suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake and that low-dose dopamine improves uptake in IPRL.

Quantitative Estimation of I-123-Iomazenil Receptor Binding in Temporal Lobe Epilepsies Using Two SPECT Acquisitions – Comparison with the Regional Cerebral Blood Flow and a Compartment Model

To compare published fractional rate constants of I-123-Iomazenil (IMZ) and C-11-Flumazenil (three-compartment/four-parameter model) with a I-123-Iomazenil receptor index calculated from two SPECT acquisitions and to compare the receptor index of the epileptogenic area with the contralateral side in patients with unilateral temporal lobe epilepsies. 28 patients were studied. 13/28 patients had a drug-resistant unilateral temporal lobe epilepsy with a successful focus localisation performed by an extensive video/EEG monitoring. 15 other patients with clinically suspected focal epilepsy and a normal MRI and IMZ SPECT scanning were used as controls. SPECT scanning was performed in all patients 15 and 100 min after intravenous injection of 111 MBq IMZ and 10 min after application of 740 MBq Tc-99m-HMPAO. Quantification of the regional uptake was performed using ROI-technique and the specific and non-specific binding of IMZ was calculated. The receptor index was calculated by the difference of the specific binding from 15 to 100 min p.i. divided by the time interval. The receptor index showed a linear correlation with recently published fractional rate constants k3 (r = 0.69 and 0.67; p = 0.15) and a moderate correlation with the k4 constant (-0.53 and -0.43; p = 0.28) by the means of C-11-Flumazenil PET and I-123-Iomazenil SPECT studies, respectively. However, statistical significance was not reached due to the few data points available from the published reports. Furthermore, the IMZ receptor index was lower in the epileptogenic area of patients with unilateral temporal lobe epilepsies compared with their contralateral side (p = 0.02; Wilcoxon-test). The IMZ receptor index showed a weak correlation with the regional cerebral blood flow independent of the evaluated region (r < 0.4; p < 0.05). The IMZ receptor index indicated to be a simple routine approach to estimate the fractional rate constant k3 (r = 0.67). The lower value of the receptor index within the epileptogenic area might be due to a lower receptor density. However in further studies, IMZ might be a helpful tool to find out subtle changes of the receptor affinity due to its approximately 30-fold higher ligand-receptor affinity compared to C-11-Flumazenil.

Carbon decomposition kinetics and nitrogen mineralization from corn, soybean, and wheat residues

An incubation study was conducted for 30 days in Taloka (fine, mixed, thermic mollic Albaqualf) and Leadvale (fine, silty, siliceous, thermic typic Fragiudult) silt loam soils to evaluate carbon (C) and nitrogen (N) mineralization from soybean [Glycine max (L.) Merr.], corn (Zea mays L.), and wheat (Triticum aestivum L.) residues. Corn and soybean residues were collected at the tasseling and late vegetative stages, respectively. Wheat straw was collected after harvest. Carbon dioxide (CO2) evolution and inorganic N accumulation were measured. Carbon mineralization was described by a sequential decomposition model with a rapid and slow phase, each described by first‐order kinetics. Rapid and slow fraction rate constants and percent rapid were determined. Decomposition ranged from 39% for wheat to 67% for soybean. Carbon dioxide evolution peaked on the third day, and 30 to 50% of residue C was decomposed during the first six days of incubation. Decomposition and N mineralization were higher in the Taloka compared to the Leadvale soil, and generally followed the sequence soybean > corn > wheat residues as did percent rapid fraction, and rapid and slow fraction rate constants. Rapid fraction rate constants ranged from 0.039±0.005 to 0.115±0.005 per day. Slow fraction rate constants ranged from 0.013±0.002 to 0.030±0.002 per day. Percent rapid fraction ranged from 13±2% to 38±2%. The half‐lives of the slow fraction ranged from 23.4±3.5 to 51.8±3.5 days. Nitrogen mineralization, as estimated by ammonium (NH4) and nitrate (NO3) formation occurred only with the soybean residue, whereas the corn and wheat residues were characterized by N immobilization throughout the study.

In Vivo Study of the Kinetics of Thiamine and its Phosphoesters in the Deafferented Rat Cerebellum

The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum on different steps of the metabolism of thiamine (Th), thiamine monophosphate (ThMP) and thiamine pyrophosphate (ThPP) were evaluated in vivo in rats. CD was carried out by i.p. injection of 3-acetylpyridine, followed by harmaline and niacinamide. SD was carried out by complete dissection of the peduncles of the left cerebellar hemisphere. Under steady state condition the radioactivity of Th and its phosphoesters was determined in plasma and whole cerebellum after an i.p. injection of thiazole-[2(14)C]-thiamine (30 micrograms:1.25 micro Ci). Analytical data were processed by using an improved mathematical compartmental model, which allowed the calculation of fractional rate constants (FRC), turnover rates (TR) and turnover times (TT). Both CD and SD caused a significant reduction of TR values for Th phosphorylation to ThPP, dephosphorylation of ThPP to ThMP and Th, and ThMP, but not Th, release. TT for all Th compounds were increased compared to controls, indicating a general slowing of thiamine metabolism in the deafferented cerebellum. These results indicate an imbalance in the thiamine metabolism resulting from the impaired activity of cerebellar neurons. The possible implications of the changes in rate of Th compound turnover with respect to biochemical changes in cerebellar ataxia are discussed.

Predicting Long‐Term Decomposition of Biosolids with a Seven‐Day Test

AbstractDecomposition of biosolids (municipal sewage sludge) in soil has been characterized by long‐term (&gt;60 d) studies. This study was conducted to determine if short‐term incubations could be used to estimate long‐term decomposition behavior. Twenty‐four biosolid/soil combinations were incubated at 25°C for a period of about 60 d. Decomposition followed first order kinetics with two fractions, rapid and slow, based on decomposability. The percentage of biosolid C in the rapid fraction (%Rapid), and the rapid and slow fraction rate constants (kr and ks, respectively) were determined using linear regression of log transformed data (sequential decomposition model) and nonlinear regression of the original data (simultaneous decomposition model). Both models adequately estimated the %Rapid, kr, and ks. The sequential model provided the best relationship between %Rapid and the percent decomposition at 7 d, %D7, and the only relationship between kr and %Rapid. The slow fraction rate constants in this study were compared to those estimated using data from other studies. The slow fraction rate constant used in prediction of long‐term decomposition was from one of these other studies. Predictions of long‐term decomposition agreed well with observed values (r2 = 0.76). It is proposed that a single measurement, %D7, could be used to assess long‐term decomposition for biosolids similar to those reported here. The equation should not be applied to biosolids with small rapid fractions (&lt;10%) such as those stored for extended periods or composted or to biosolids not originating from municipalities.

Insulin secretion and plasma levels of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 [7–36 amide] after oral glucose in cirrhosis

A blunted initial insulin secretory response may contribute to oral glucose intolerance in cirrhosis. Oral glucose is a better stimulant to insulin secretion than intravenous (IV) glucose in part because of release of gut peptides, notably glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 [7–36 amide] (GLP-1 [7–36 amide]). Because impaired release of or resistance to these gut peptides could explain impaired insulin secretion after oral glucose, we measured insulin secretion, plasma GIP, and GLP-1 [7–36 amide] levels, basally and after 75 g oral glucose, in 10 cirrhotics and 10 controls. Insulin secretion was calculated from a two-compartment analysis of serum C-peptide levels using kinetic parameters derived from IV injection of recombinant human C-peptide. C-peptide metabolic clearance rate, and the fractional rate constants for C-peptide (using the two-compartment model) were not significantly different, but the volume of the central compartment was 15% greater in cirrhotics ( P < .01). Fasting blood glucose levels were similar (cirrhotics, 4.9 ± 0.2; controls, 4.6 ± 0.1 mmol/L) but serum insulin was six times higher in cirrhotics ( P < .001). Cirrhotics had higher fasting GIP (215 ± 72 vs. 42 ± 18 pmol/L) and GLP-1 [7–36 amide] levels (25 ± 3 vs. 16 ± 1 pmol/L) (both P < .05). After oral glucose, blood glucose levels were significantly higher in cirrhotics. The timing of the gut peptide response to oral glucose was similar in the two groups, but peak levels of both peptides were ∼x2 higher in the cirrhotics. For the 1st 30 minutes, C-peptide levels and insulin secretion were similar in the two groups. In controls, insulin secretion peaked at 20 to 25 minutes and coincided with the GLP-1 [7–36 amide] peak; insulin secretion then decreased despite a persistent elevation in plasma GIP and glucose levels. In cirrhotics, peak insulin secretion was delayed until 50 to 55 minutes (coincident with the glucose peak). Total insulin secretion during the 4 hours after glucose ingestion was 55% higher in the cirrhotics, but peak insulin secretion rates were similar despite higher gut peptide and glucose levels in cirrhotics. The study shows that, after oral glucose, cirrhotics have a blunted serum C-peptide response and insulin secretion rate. This is not attributable to reduced levels of GIP or GLP-1 [7–36 amide] but could be attributable to resistance to their action.

Insulin secretion and plasma levels of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 [7-36 amide] after oral glucose in cirrhosis

A blunted initial insulin secretory response may contribute to oral glucose intolerance in cirrhosis. Oral glucose is a better stimulant to insulin secretion than intravenous (IV) glucose in part because of release of gut peptides, notably glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 [7-36 amide] (GLP-1 [7-36 amide]). Because impaired release of or resistance to these gut peptides could explain impaired insulin secretion after oral glucose, we measured insulin secretion, plasma GIP, and GLP-1 [7-36 amide] levels, basally and after 75 g oral glucose, in 10 cirrhotics and 10 controls. Insulin secretion was calculated from a two-compartment analysis of serum C-peptide levels using kinetic parameters derived from IV injection of recombinant human C-peptide. C-peptide metabolic clearance rate, and the fractional rate constants for C-peptide (using the two-compartment model) were not significantly different, but the volume of the central compartment was 15% greater in cirrhotics (P < .01). Fasting blood glucose levels were similar (cirrhotics, 4.9 +/- 0.2; controls, 4.6 +/- 0.1 mmol/L) but serum insulin was six times higher in cirrhotics (P < .001). Cirrhotics had higher fasting GIP (215 +/- 72 vs. 42 +/- 18 pmol/L) and GLP-1 [7-36 amide] levels (25 +/- 3 vs. 16 +/- 1 pmol/L) (both P < .05). After oral glucose, blood glucose levels were significantly higher in cirrhotics. The timing of the gut peptide response to oral glucose was similar in the two groups, but peak levels of both peptides were approximately x2 higher in the cirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)