Decrease In Clearance Rate Research Articles

Effect of yellow loess on clearance rate in seven species of benthic, filter-feeding invertebrates

Attempts have been made, especially in Asia, to displace harmful algal blooms (HABs) by spraying ‘china clay’ and ‘loess’ over affected coastal waters. The impact of this technique on benthic communities and processes is not known. We examined the effects of yellow loess on clearance rates of the benthic, filter-feeding invertebrates, Crassostrea virginica (Gmelin 1791), C. gigas (Thunberg 1793), Mytilus edulis (Linnaeus 1758), M. trossulus (Gould 1850), Argopecten irradians (Lamarck 1819), and Crepidula fornicata (Linnaeus 1758). An Obelia species of hydroid was also studied and the percent time open was analysed. Depletion rates were measured using a range of loess concentrations suspended in culture with unicellular algae (Rhodomonas lens) in 0.45 μm filtered seawater. The effects of loess on clearance rates and behaviour were species-specific. C. virginica was not impacted until clay concentrations reached 1.0 g L−1, while A. irradians showed a significant decrease at 0.01 g L−1. M. edulis showed a significant decrease in clearance rates at the 1 and 10 g L−1 concentrations. For hydroids, the percent time open was significantly lower than the control at 0.01, 0.1, and 10 g L−1. We clearly demonstrate that loess has a significant negative impact on filter-feeding invertebrates. The use of clay as a strategy for mitigation of HABs should be approached with extreme caution. While the control of active blooms may eventually be possible, it may not necessarily be an environmentally advisable or responsible approach to dealing with HABs.

Effects of suspended and sedimented clays on juvenile hard clams, Mercenaria mercenaria , within the context of harmful algal bloom mitigation

Increased interest in using ecologically inert clays to flocculate, sediment, and thus mitigate harmful algal blooms at nearshore mariculture sites has prompted studies on the effectiveness of this method on prolific blooms, such as those caused by the neurotoxic dinoflagellate Karenia brevis in the Gulf of Mexico. Potential repercussions of this control strategy revolve around the increased flux of suspended particles to the benthos. Juvenile suspension-feeding bivalves are potentially vulnerable as they could suffer burial, a decrease in clearance rates, and/or an increase in pseudofeces production in response to suspended clay, leading to reduced growth and delay in attaining size refuge from predators. Here we assess lethal and sublethal effects on juvenile hard clams, Mercenaria mercenaria, in a 2-week flume application of phosphatic clay to simulated blooms of the nontoxic dinoflagellates Heterocapsa triquetra and Prorocentrum micans. Flow regimes simulated two contrasting, “worst-case” field conditions where (1) low flow allowed complete sedimentation and formation of a benthic sediment layer, and (2) high flow allowed complete particle suspension. No clam mortalities occurred in either treatment. The sedimentation treatment showed variable growth inhibition in shell and/or tissue, but effects were not apparent compared to controls (no sediment layer), and clams rapidly resumed siphon contact with the overlying water column. In contrast, a strong growth effect (~90% reduction in shell and tissue growth) occurred in particle-suspension trials compared to no-clay controls. These results suggest that repeated clay applications in the field are likely more detrimental to clams in a high-energy environment leading to prolonged in situ resuspension of clay than in an environment favoring sedimentation.

In vivo evaluation of interaction between aqueous seed extract of Garcinia kola Heckel and ciprofloxacin hydrochloride.

The effect of Garcinia kola seed extract (100 mg/kg) on the pharmacokinetic and antibacterial effects of ciprofloxacin hydrochloride (40 mg/kg) was studied. The results (mean +/- SEM) indicated that concurrent administration of both agents significantly (P < 0.05) decreased average serum concentration, peak serum concentration, and elimination rate of ciprofloxacin HCl, whereas the half-life and clearance rate were increased. The decrease in clearance rate was not significant. There was no difference in time to peak plasma concentration of ciprofloxacin HCl in both groups (n = 5), which occurred at 1 hour. However, the peak plasma concentration of ciprofloxacin HCl was 46.90 +/- 9.50 microg/mL in the group that received ciprofloxacin HCl alone as against 35.80 +/- 9.30 microg/mL noted in the group that received both agents (difference of 22.24%). At 2.5 hours and longer, the values were higher in the group that received both agents, but these were not statistically significant. The reciprocal serum inhibitory titer (SIT) was 33.33 and 50.00% higher in group that received ciprofloxacin HCl alone at 1 and 2.5 hours, respectively; the highest value for both groups being at 1 hour. In contrast, at 4 hours, the value of reciprocal SIT was 66.67% higher in the group that received both agents and at 24 hours, the value was zero for both groups. The observed pharmacokinetic and antibacterial interactions at various time interval indicate biphasic interaction. The interaction was antagonistic at 1 and 2.5 hours, but exhibited potentiation at 4 hours. The precise mechanism underlying the observed biphasic interaction is not fully understood.

Influence of plasma triglyceride and plasma cholesterol levels on the clearance rate of fibrinogen.

Increased plasma levels of fibrinogen are associated with a higher risk of cardiovascular disease. It has been suggested that lipid levels may influence the fibrinogen levels by a mechanism other than the synthesis rate, for example a decreased clearance rate. We performed a pilot study to explore this possibility. Twelve male Wistar rats were fed for four weeks with a control low fat/low cholesterol diet, a high fat/high cholesterol diet, and a high fat/high cholesterol diet with an additional 0.5% cholic acid. Labeled 125I fibrinogen was injected, and blood was sampled repeatedly. From the plasma radioactivity of the samples, fibrinogen halflife time was calculated for each animal. Our results suggest that plasma lipids lengthen the fibrinogen halflife times, although the differences were not statistically significant in this small study. Our final conclusion from this study is that lipids may have an effect on the turnover rate of fibrinogen and possibly affect fibrinogen levels through this mechanism.

Effects of toxic and non-toxic cyanobacteria on grazing, zooplanktivory and survival of the mysid shrimp Mysis mixta.

We measured the effect of toxic and non-toxic cyanobacteria strains on grazing, predation rates and survival of the mysid shrimp Mysis mixta by means of laboratory experiments. Juvenile and adult M. mixta fed most actively on the non-toxic strains Aphanizomenon flos-aquae and Nodularia sphaerocarpa as on high quality food, the green flagellate Brachiomonas submarina, whereas grazing on the toxic N. spumigena was significantly lower than on the other strains. The mysids showed normal functional responses; decreasing clearance rates at increasing concentrations of cyanobacteria. In a separate predation experiment, the feeding rates on copepods declined in the presence of aggregated non-toxic cyanobacteria. However, we could not demonstrate increased mortality in a 7-week experiment where mysids were exposed to high concentrations of toxic N. spumigena

Feeding activity, retention efficiency, and effects of temperature and particle concentration on clearance rate in the marine bryozoan Electra crustulenta

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 215:133-141 (2001) - doi:10.3354/meps215133 Feeding activity, retention efficiency, and effects of temperature and particle concentration on clearance rate in the marine bryozoan Electra crustulenta Dennis Lisbjerg, Jens Kjerulf Petersen* National Environmental Research Institute, PO Box 358, Frederiksborgvej 399, 4000 Roskilde, Denmark *Corresponding author. E-mail: jkp@dmu.dk ABSTRACT: Various factors influencing clearance rate were elucidated on the bryozoan Electra crustulenta (Pallas). Measurements of clearance rates were performed using the algae Rhodomonas sp. (6 µm in diameter). Clearance rates were related to the area of the active zooids within the colonies in order to obtain area-specific clearance rates. Specific area was 42% of the total colony area. Several replicates were performed with each colony to obtain maximum clearance rate (Fmax). Fmax increased with temperature from 90 ml h-1 cm-2 at 6°C to 229 ml h-1 cm-2 at 22°C. Clearance rate decreased at increasing algal cell concentration from 1600 to 19000 cells ml-1. The decrease in clearance corresponded to a maximum ingestion rate at particle concentrations >8500 Rhodomonas sp. cells ml-1. E. crustulenta zooids are capable of retaining and ingesting particles in the range from ca 5 to ca 30 µm in diameter. Smaller particles are less efficiently retained due to the structure of the feeding apparatus, the lophophore and larger particles due to the size of the mouth (30 µm in diameter). Feeding activity was observed on single zooids and it was found that zooids have periodical retraction of the lophophore. At low particle concentrations (ca 1500 cells of Rhodomonas sp. ml-1) the lophophore is retracted 5 x h-1 for periods of 38 s. Zooidal activity measured as the time of protruded lophophore thus leads to an activity of 95% of the total time. At high algae concentrations, zooidal feeding activity decreased to 70% as the lophophore was retracted more frequently (10 x h-1) and for longer periods of time (107 s). Despite the decreased activity at high algae concentration, this could only account for 50% of the decrease in clearance rate. Thus, regulatory mechanisms of the clearance rate other than retraction of the lophophore must be considered in bryozoans. KEY WORDS: Clearance rate · Feeding activity · Filtration · Functional response · Ingestion rate · Particle spectrum · Regulation of filtration rate · Retention efficiency Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 215. Online publication date: May 31, 2001 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2001 Inter-Research.

Effect of chemotherapy on pulmonary epithelial permeability in lung cancer

The aim of this study is to investigate the effect of one-course chemotherapy on the pulmonary epithelial permeability. Eighteen patients (18 male; mean age: 59±10 years) with lung cancer (11 non-small cell, 7 small cell) inhaled 40 mCi (1,480 MBq) 99mTc-diethylenetriaminepentaacetic acid (DTPA). Thirty images of 1-min duration were acquired from posterior projection. The first 7 min of the decay-corrected time activity curves were used to calculate lung clearance half-time. Clearance half-times of 99mTc-DTPA from the peripheral regions of the lungs were 42 ± 19 min before and 56±34 min after chemotherapy ( p =0.009 ); from the central regions, clearance half-times were 112±94 min before and 160±125 min after chemotherapy ( p =0.005 ). This decrease in clearance rate might be related to decreasing mucociliary clearance rate due to the toxic effect of the chemotherapy regimen on cilia movement and/or mucus structure. 99mTc-DTPA radioaerosol study can be used to monitor the toxic effects of chemotherapy on the pulmonary epithelium and possibly on mucociliary function.

HSP70 levels in physiologically stressed Baltic Sea mussels

Mussels, Mytilus edulis L., from the Baltic Sea were exposed to stressful cadmium and temperature environments. The expression of the 70 000 kD heat shock protein family (HSP70) and of several organismal responses was observed in two phases. Mussels exposed to 20 °C for one day had higher levels of HSP70 than controls at 4 °C, with 20 μg litre −1 cadmium or without cadmium. The higher temperature increased respiration and ammonia excretion and decreased clearance rate and scope for growth. In the second phase, mussels pretreated at 20 °C for 5 days and reacclimated to 4 °C for 5 days still showed significantly elevated HSP70, with 20 μg litre −1 cadmium and without cadmium. The organismal responses in the second phase were much less affected by treatment, although scope for growth declined in pretreated animals exposed to cadmium. HSP70 seems to be a suitable indicator of both present and recent stress. A functional relationship between HSP70 levels and adaptation to heat and cadmium is suggested but not established.

Neurotoxic Lesions Induced by Monosodium Glutamate Result in Increased Adenopituitary Proopiomelanocortin Gene Expression and Decreased Corticosterone Clearance in Rats

Hypothalamic-pituitary-adrenocortical function in rats with brain lesions induced by neonatal monosodium glutamate (MSG) treatment (4 mg/g, 5 administrations, i.p.) was evaluated in the present study. Using in situ hybridization we found increased proopiomelanocortin (POMC) mRNA levels in the adenopituitary and normal corticotropin-releasing hormone mRNA levels in the hypothalamic paraventricular nucleus in MSG-treated rats. The total content of pituitary adrenocorticotropin (ACTH) was not changed, while pituitary ACTH concentration was higher in MSG-treated compared to control rats. The number of ACTH-immunostained cells per a constant area of adenohypophysial section, as measured by immunohistochemistry, was unchanged indicating that no significant condensation of corticotropes occurred. Basal plasma ACTH concentrations were not different, whereas morning corticosterone levels were elevated in rats with MSG treatment. While ACTH response to stress stimuli was similar in both groups of rats, corticosterone response to exogenous ACTH (500 ng/kg, i.v., Synacthen), short-lasting handling and immobilization was of the same magnitude but prolonged in MSG-treated rats. Based on the decline of [³H]corticosterone in plasma, a decreased corticosterone clearance rate was found in MSG-treated rats. These findings suggest that MSG treatment results in increased POMC gene expression per corticotrope of the atrophic pituitary resulting in maintenance of normal pituitary ACTH stores and plasma ACTH levels. Elevated basal levels of corticosterone in plasma as well as prolonged corticosterone responses to stimulations in rats treated with MSG seem to be due to a decreased clearance rate of corticosterone.

Feeding behaviour of Centropages typicus in calm and turbulent conditions

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 168:109-118 (1998) - doi:10.3354/meps168109 Feeding behaviour of Centropages typicus in calm and turbulent conditions Philippe Caparroy*, M. T. Pérez, François Carlotti Station Zoologique, URA 2077, BP 28, F-06230 Villefranche-sur-Mer, France *Present address: Danish Institute for Fisheries Research, Department of Marine and Coastal Ecology, Kavalergården 6, DK-2920 Charlottenlund, Denmark. E-mail: caparroy@ccrv.obs-vlfr.fr ABSTRACT: Feeding of the copepod Centropages typicus on the oligotrich ciliate Strombidium sulcatum was studied in the laboratory under controlled, measured conditions of grid generated small scale turbulence. High levels of turbulence, ε (kinetic energy dissipation rate) = 2.9 x 10-2 to 3 × 10-1 cm2 s-3, increased the clearance rate of C. typicus feeding on S. sulcatum by up to a factor of 4 in comparison to calm water values. At a level of turbulence of 4.4 cm2 s-3, we observed a drastic decrease in clearance rates to values equivalent to those in calm water. We suggest an explanation for the observed changes in predation rates with levels of turbulence. Video recorded observations of the behaviour of free swimming C. typicus conducted in calm conditions suggest that the copepod uses a cruising strategy to search and encounter S. sulcatum. In the presence of this ciliate, C. typicus increases the proportion of time spent swimming at a mean velocity of 3.5 mm s-1: from 49.5% in filtered seawater without ciliates to 79.5% in the presence of S. sulcatum (1 cell ml-1). Furthermore, a qualitative change of the swimming behaviour is triggered by the presence of the ciliate, resulting in an increased proportion of time spent slow swimming in a Œhelical¹ mode. Our results suggest that high levels of small scale turbulence substantially increase predation rates of cruising copepods. KEY WORDS: Turbulence · Predation · Swimming · Behaviour · Strombidium sulcatum · Centropages typicus Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 168. Publication date: July 09, 1998 Print ISSN:0171-8630; Online ISSN:1616-1599 Copyright © 1998 Inter-Research.

Grazing on autotrophic and heterotrophic picoplankton by ciliates isolated from Lake Kinneret, Israel

The rates of ingestion of three ciliates ( Colpoda steinii , Cyclidium sp. and Srylonichia sp.) on fluorescently labeled heterotrophic bacteria, picocyanobacteria ( Synechococcus P, CN) and a picoeukaryote isolated from Lake Kinneret were measured. Uptake values were 930, 35 and 1210 bacteria ciliate (cil) −1 h −1 for Colpoda , Cyclidium and Sylonichia , respectively, depending on prey concentrations. An increase in prey concentration resulted in a decrease in clearance rates from 405 to 32 nl cil −1 h −1 . Clearance rates of Colpoda fed on Synechococcus (P. CN) and on picoeukaryotes ranged from 27 to 62 and from 3 to 7 nl cil −1 h −1 , respectively. Cyclidium , which is classified as a picoplankton feeder, showed lower clearance rates when fed on Synechococcus P and bacteria. Specific clearance (body volume cell −1 h −1 for the three ciliates studied decreased when prey supply increased, for all three food sources. Relating to body volume, Colpoda could manage successfully on bacteria as its sole food source. It appears from our measurements that bacteria in Lake Kinneret are abundant enough to sustain the carbon requirements of Colpoda .

Environmental pollution caused elevated concentrations of oestradiol and vitellogenin in the female flounder, Platichthys flesus (L.)

Female and male flounder, Platichthys flesus, were exposed to various concentrations of polluted harbour dredged spoil in large mesocosms for up to 3 years. The dredged spoil contained a mixture of contaminants representative of pollution concentrations found in the natural environment. Ovarian development, vitellogenesis and steroid hormones in the fish were studied and compared with results from feral fish sampled at a relatively clean field site in the Dutch Wadden Sea. Plasma concentrations of vitellogenin (VTG), established by densitometry in sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, fluctuated during the annual reproductive cycle of the Wadden Sea flounder and reached a maximum during autumn and winter (advanced vitellogenesis). Fish held in the polluted mesocosm for 3 years exhibited premature vitellogenesis, resulting in a high number of oocytes in the yolk granule stage in spring, normally the previtellogenic period of the year. Moreover, VTG was significantly elevated in the plasma of these females relative to the concentrations in fish from the reference mesocosm. The high concentration of plasma VTG in females from the polluted mesocosm coincided with significantly elevated concentrations of testosterone and 17β-oestradiol. The in vitro ovarian production capacity of these steroids, however, was not altered. In feral and pollution-exposed male flounder, no VTG was detected. On the basis of these findings, it was concluded that premature vitellogenesis in the female flounder was a result of elevated 17β-oestradiol concentrations rather than a direct endocrine effect of xeno-oestrogenic contaminants. It is suggested that the elevated 17β-oestradiol concentrations are caused by decreased clearance rates of steroids in the blood.

Filtration and absorption of Phaeocystis cf. globosa by the mussel Mytilus edulis L.

Mussels, Mytilus edulis L., were exposed to natural seawater, supplemented with variable amounts of Phaeocystis cf. globosa solitary cells and colonies and to a reference diet consisting of natural seawater, supplemented with Phaeodactylum tricornutum. Clearance rate showed a linear decrease with the amount of colonies present, expressed as total ‘circular equivalent surface area’. Extension of the exposure period for 28 h resulted in a further decreased clearance rate. Recovery of the clearance rate began immediately after exposure to untreated natural seawater. In the absence of colonies, there was a moderate clearance rate reduction. Filtration at reduced clearance rates was not compensated by increased particle concentrations and no adaptative response to the diet was observed. In an earlier experiment, we observed that the absorption efficiency of ingested Phaeocystis diet was not significantly different from the reference diet. It is concluded that the adverse effects of Phaeocystis blooms are mainly determined by the total colony surface area. There is no adaptation over time to diets with colonies. Once ingested, Phaeocystis is absorbed normally and has significance as food.

Atrial natriuretic factor secretion: a role for atrial systolic ejection force?

The increase in plasma concentration of atrial natriuretic factor in heart transplant patients has not been fully elucidated. Besides an eventual pressure or volume overload leading to passive atrial distension, the atrial tension developed during atrial systole, or atrial ejection force, which may be increased by the transplantation procedure, is an important determinant of atrial natriuretic factor release. We therefore determined the plasma concentration of atrial natriuretic factor and the maximal atrial ejection force in 15 heart transplant patients and 8 controls, matched for age and body mass. Atrial ejection force, as defined as the force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, was obtained using combined two-dimensional imaging and doppler echocardiography. Serum creatinin concentrations, heart rate [91.9 (SD 13.2) vs 71.8 (SD 10.9) beats.min-1], mean arterial blood pressure [103.9 (SD 9.8) vs 87.4 (SD 5.8) mmHg, 13.85 (SD 1.31) vs 11.65 (SD 0.77) kPa], left ventricular posterior wall thickness and interventricular septum thickness were higher in heart transplant patients compared to controls. Plasma concentration of atrial natriuretic factor was also elevated in heart transplant patients [63.9 (SD 18.1) vs 34.0 (SD 3.2) pg.ml-1; P < 0.001]. In contrast, although the left atrial area was greater in heart transplant patients [28.2 (SD 4.8) vs 15.8 (SD 2.5) cm2; P < 0.001], mitral area, transmitral Doppler A-wave maximal velocity and atrial ejection force were similar in transplant and in control patients [7.7 (SD 3.5) vs 8.9 (SD 2.8) kdyn, 77 (SD 35) vs 89 (SD 28)mN]. No significant correlation was observed between concentration of atrial natriuretic factor and atrial ejection force, either in heart transplant patients or in controls. Thus, the elevated plasma concentration of atrial natriuretic factor observed in these heart transplant patients was multifactorial in origin, and was considered to depend upon an hypersecretion rather than upon a decreased clearance rate. Moreover, it is suggested that the atrial ejection force was unlikely to have participated in this enhanced release of atrial natriuretic factor.

Modulation of very low density lipoprotein production and clearance contributes to age- and gender- dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice.

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been studied to identify factors modulating chylomicron and VLDL remnant lipoprotein metabolism. Transient elevated levels of VLDL/LDL-sized lipoproteins occurred in these mice with maximal levels during the period of rapid growth (optimum at 45 d of age). After about 100 d of age, serum cholesterol and triglyceride levels stabilized to slightly elevated levels as compared to control mice. The expression of the APOE*3-Leiden transgene was not age-dependent. In young mice the in vivo hepatic production of VLDL-triglycerides was 50% increased as compared to older mice. This is sustained by in vivo VLDL-apo B turnover studies showing increased (75%) VLDL-apo B secretion rates in young mice, whereas the VLDL-apo B clearance rate appeared not to be age dependent. On a high fat/cholesterol diet, females displayed significantly higher cholesterol levels than males (10 versus 7.0 mmol/liter, respectively). Serum levels of VLDL/LDL sized lipoproteins increased upon administration of estrogens, whereas administration of testosterone gave the opposite result. As compared to male mice, in female mice the hepatic VLDL-triglyceride production rate was significantly elevated. Injection of estrogen in males also resulted in increased VLDL-triglyceride production, although not statistically significant. In vivo VLDL-apo B turnover experiments showed that the VLDL secretion rate tended to be higher in females. Although, the fractional catabolic rate of VLDL-apo B is not different between males and females, administration of estrogens in males resulted in a decreased clearance rate of VLDL, whereas administration of testosterone in females resulted in an increased clearance rate of VLDL. The latter presumably due to an inhibiting effect of testosterone on the expression of the APOE*3-Leiden transgene. We conclude that hyperlipidemia in APOE*3-Leiden transgenic mice is strongly affected by age via its effect on hepatic VLDL production rate, whereas gender influences hyperlipidemia by modulating both hepatic VLDL production and clearance rate.

Plasma epinephrine appearance and clearance rates in fetal and newborn sheep

Newborn plasma catecholamine levels are elevated compared to fetal life. Whether this reflects increased catecholamine secretion after birth or decreased clearance is not known. To determine the plasma appearance and clearance rates for catecholamines during the transition to postnatal life, we compared plasma epinephrine appearance and clearance rates in fetal sheep before birth and in newborns after delivery. Plasma epinephrine appearance and clearance rates were measured by radiotracer analysis in eight fetuses at 127 +/- 1 days of gestation and, after cesarean delivery, at 130 +/- 1 days of gestation. There was no difference in plasma epinephrine appearance rate during the fetal (26 +/- 4 ng.kg-1 x min-1) or newborn studies (31 +/- 5 ng.kg-1 x min-1). The fetal plasma epinephrine clearance rate (131 +/- 13 ml.kg-1 x min-1) was significantly higher than newborn plasma epinephrine clearance rate (40 +/- 3 ml.kg-1 x min-1). Thus fetal plasma epinephrine appearance rate is not different from appearance rate in the immediate newborn period when catecholamine levels are higher than during most other physiological circumstances. The increase in circulating catecholamine levels at birth is due in part to a significant decrease in clearance rate. It is likely that removal of the placental contribution to whole body clearance accounts for much of the difference observed in fetal and newborn clearance rates.

The Level of γ-Glutamyltransferase in Serum, Effect of Carbohydrate Heterogeneity on Clearance Rate

The measurement of serum gamma-glutamyltransferase (GT) is a frequently used parameter of liver diseases. The serum enzyme originates from liver and is cleared from the circulation by the galactose receptor in liver. The rate of uptake will thus vary with the amount of terminal galactose residues on the enzymes' carbohydrate moiety. Using an experimental rat model we have studied the relative clearance rates of variant forms of GT with different carbohydrate composition. GT purified from pancreas and kidney contains less sialic acid and showed considerably higher clearance rates than the enzyme from liver. The rapid uptake of the kidney and pancreas enzymes indicates that these enzymes may not reach detectable levels if released from these organs to the circulation. On the other hand, GT in serum of alcoholics contains increased amount of sialic acid and this enzyme variant showed a slightly decreased clearance rate compared to the normal liver enzyme. Increased sialylation of GT may thus contribute to the increased level of the enzyme in serum after alcohol abuse.

Increased serum stability and prolonged biological half-life of neocarzinostatin covalently bound to monoclonal antibodies.

The pharmacokinetics of neocarzinostatin (NCS) have been compared to NCS conjugates with monoclonal antibodies using Balb/c and tumor bearing nude mice. Data on blood and whole body clearance revealed that the high MW conjugate persists in the body far longer and at a higher level than the free drug. Excretion of the free drug occurs with an extremely rapid renal clearance and localization of the remaining drug in the kidney, whereas the NCS immunoconjugate remained in circulation far longer allowing time for tumor localization to occur without renal accumulation of drug. In addition, NCS conjugated to monoclonal antibody was found to retain its activity in human serum better than free drug, in agreement with data obtained for other NCS-derivatives. Half-time of inactivation was greatly extended when measured under relevant conditions in a DNA strand-break assay. The results indicate that two of the most important requirements for the successful targeting of NCS in vivo, decreased clearance rate and increased serum stability are achieved by conjugation to antibody. Both results increase the probability of NCS accumulating in tissue while still in its active form. Coupling of NCS to monoclonal antibody decreases clearance and inactivation rate and increases localization of the active drug in tumor tissue.

Endothelin in Patients with Chronic Renal Failure

To investigate the pathophysiological significance of endothelin-1 (ET-1) in renal failure, we measured plasma and urine concentrations of ET-1-like immunoreactivity (LI) by radioimmunoassay (RIA). The plasma ET-1-LI level was significantly increased in hemodialyzed and nonhemodialyzed patients with chronic renal failure (CRF). The increase in the plasma ET-1-LI level in CRF was much larger than that in other diseases in which the plasma ET-1-LI level was reported to be increased. The urine ET-1-LI level was lower, and daily excreted amounts of ET-1-LI were smaller in CRF patients than in normal subjects. These findings indicate that the increased plasma level of ET-1-LI in CRF results from the decreased clearance rate of ET-1-LI in the kidney. Gel permeation chromatographic analysis revealed that ET-1-LI in plasma from CRF consisted of small and large molecular forms of ET-1-LI. The small molecular form is presumably ET-1, and large molecular forms are big ET-1 and another component with the molecular weight of 6,000 as is the case of that in normal plasma (1). However, the ratio of the smaller to large molecular forms of ET-1-LI in CRF was 1:13 and was quite different from that in normal plasma (1:4). These observations clearly indicate that the elevation of plasma ET-1-LI level in CRF was mainly due to the increase in the large molecular form of ET-1-LI.

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)