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Biomedical subjects

L Mor

Publications and source records attributed to L Mor.

16 recordsLinked to original sources

Pulmonary angiotensin converting enzyme activity in elastase induced emphysema.

Pulmonary emphysema would be expected to reduce angiotensin converting enzyme (ACE) activity due to diminished capillary bed. However, transpulmonary angiotensin conversion has been found to be unaffected or marginally reduced in emphysema. In the present study we examined the activity of ACE in an experimental model of emphysema. Vmax and Km of ACE were determined in lung homogenates of six hamsters with elastase-induced emphysema and seven control hamsters. In the emphysematous lungs, ACE activity was significantly elevated due to marked increase in Vmax (19.2 +/- 1.7 vs. 4.9 +/- 1.6 nmol/min/mg protein for emphysematous and control lungs, P < 0.01). The Km of ACE was unaffected by emphysema. We suggest that the increase in ACE activity may be an adaptive change to enable adequate metabolic activity in the face of progressive reduction in pulmonary capillary surface area in emphysema.

Amino Acid Sequence↗

Transplacental transfer of ritodrine and its effect on placental glucose and oxygen consumption in an in vitro human placental cotyledon perfusion.

Maternofetal transfer of ritodrine and its effect on placental glucose and oxygen consumption were studied using a recycling perfusion of maternal and fetal circulations of an isolated cotyledon of a term human placenta. 3H-labeled ritodrine was introduced into the maternal side of the perfusion system. Transfer was calculated from the linear rise of ritodrine concentrations on the fetal side and was found to be 7.31 +/- 1.02 ng/g placental wet weight/min (SEM) when 1.4 micrograms/ml of ritodrine was used (n = 3) and 14.7 +/- 1.06 ng/g placental wet weight/min when the concentration was 2.8 micrograms/ml (n = 5). The antipyrine transfer rate, 4.1 +/- 0.51 mg/kg/min (n = 8), was used to demonstrate perfusion adequacy and served as an internal standard. Upon computing the mass balance of ritodrine and antipyrine at the end of the experiment, it was found that 17% of ritodrine disappeared from the perfusion system compared to 0.7% of antipyrine (p less than 0.01). The introduction of ritodrine into the perfusion system did not affect placental glucose and oxygen consumption rates of 0.35 +/- 0.01 mumol/g/min (n = 7) and 0.19 +/- 0.013 mumol/g/min (n = 5), respectively.

Antipyrine↗

Angiotensin-converting enzyme activity in the isolated perfused guinea pig lung.

We have developed a pressure-dependent isolated lung perfusion system that can be used for the determination of pulmonary enzyme activity and kinetics under physiologic conditions. This development was done using two different artificial radiolabeled substrates, glycine-1-hippuryl-L-histidyl-L-leucine and phenyl-4(n)-hippuryl-glycyl-glycine, for the pulmonary enzyme, angiotensin-converting enzyme. With this system, we assessed the effects of different perfusate types upon the stability of the perfusion as well as the independent effects of pressure, flow, and substrate concentration on the activity of this enzyme. We concluded that this system enables the operator to determine the kinetics and activities of pulmonary enzymes independently of the effects of pressure and flow in a perfusion system that is stable for at least 3 h under physiologic conditions.

Animals↗

Does insulin affect placental glucose metabolism and transfer?

An in vitro recycled perfusion of the human placenta was used to investigate the effect of insulin on placental metabolism and transfer of glucose. Human insulin, 1000 microU/ml, was introduced into either maternal or maternal and fetal compartments. In one series of experiments placentas were used as either a control group or study group, whereas in the other series each placenta served as its own control. Metabolic effects were determined by measuring placental glucose and oxygen consumption and lactate production rate. The effect of insulin on transfer was studied by the use of 3-O-methylglucose labeled with tritium; this effect was expressed as the slope of maternal minus fetal concentrations on a natural logarithmic scale and compared with the antipyrine tagged with carbon 14. The stability of perfusate volume was used as an index for placental integrity, whereas absence of tissue edema demonstrated adequacy of perfusion. Neither of the metabolic parameters studied was significantly affected by insulin, and insulin did not have an effect on 3-O-methylglucose transfer rate. It was concluded that, in contrast to other tissues in the body, placental glucose metabolism and transfer are not sensitive to the action of insulin.

3-O-Methylglucose↗

Renal bilirubin excretion in canine models of jaundice.

Renal handling of bilirubin and its relationship to blood bilirubin level were investigated for up to 2 weeks in two models of jaundiced dogs, namely, chronic bile duct ligation (CBDL), which are mildly icteric, and choledococaval anastomosis (CDCA), which develop deep jaundice. The mean (+/- SD) urinary bilirubin excretion in CBDL plateaued at 30.3 +/- 9.3 mg/24 hr whereas in CDCA it continued to increase above the normal bilirubin production rate (56-84 mg/24 hr) up to 130-150 mg/24 hr. The renal clearance of bilirubin in both models was inversely proportional to serum bilirubin concentration. It was approximately twice as high in the CDCA model, which induced also a moderate diuresis. It is suggested that higher serum bilirubin levels in CDCA dogs is due to the increased production of bilirubin which is not compensated by the renal clearance of bilirubin.

Animals↗

Serum bilirubin constituents in different experimental models of conjugated hyperbilirubinemia.

The object of the study was to explain the differences in bilirubin level in various experimental jaundice models. The Bil constituents in conjugated hyperbilirubinemic dog models were identified. Total Bil was measured using the Jendrassik and Grof method and direct spectrophotometry. Conjugated and unconjugated Bil were measured using the Weber-Schalm extraction method. Bilirubin covalently bound to albumin was measured indirectly from the total Bil and the non-CBBA fraction. The non-CBBA was estimated either as the sum of the CB and UCB concentrations determined by the W-S method or as the nonprecipitated fraction after deproteinization with ammonium sulfate-saturated ethanol when using DS. The TB, CB, UCB, and CBBA levels were compared in two hyperbilirubinemic dog models: chronic bile duct ligation (CBDL) and internal choledochocaval anastomosis (CDCA). The mean TB in internal CDCA (16.5 +/- 3.67 mg%) was significantly higher than in CBDL (3.4 +/- 1.75 mg%). Most of the serum Bil in these two models was conjugated, 13.4 +/- 2.24 and 3.2 +/- 1.7 mg%, respectively. No CBBA was found in the CBDL or in the partially obstructed internal-CDCA dogs. The TB in an external-CDCA model was essentially similar to the internal-CDCA model. The indirect Bil level in the external-CDCA model was six to seven times higher than the UCB level, and the CBBA level varied between 30 and 80% of the TB. Up to 50% CBBA was found also in patients with intra- or extrahepatic cholestasis. The findings indicate that, unlike the commonly assumed hypothesis, the serum TB level in the CDCA models, which was higher than in the CBCL one, is not due to high UCB levels. Rather, hyperbilirubinemia in the external-CDCA model is due to increased levels of CBBA or, perhaps, to variations in the amount and/or composition of CB entering the blood and cleared by the kidney.

Animals↗

Tailor-made agarose-based reactive beads for hemoperfusion and plasma perfusion.

Composite beads of approximately 1 mm diameter, made of crosslinked agarose and containing Fuller's Earth or zirconium oxide powders, were prepared and used in extracorporeal systems for blood detoxification. The former was used for the removal of Paraquat, while the latter was used to remove inorganic phosphate from hyperphosphatemic animals with or without acute renal failure. The high surface area of the powder, combined with the low resistance to diffusion in the crosslinked agarose matrix, are highly advantageous. The crosslinking provides high mechanical strength, heat stability, prolonged shelf life, good blood flow characteristics, and prevents the release of fine particles into the blood. Crosslinked agarose beads of 1 mm diameter, containing chemically-bound heparin were also prepared, and used as a model for direct contact removal of LDL-cholesterol from the blood of familial hypercholesterolemic patients by hemoperfusion. The high capacity of these beads (over 5 mg LDL/mL beads) indicates that this clinical modality can replace the highly expensive plasmapheresis procedure presently used.

Animals↗

Controlling anticoagulation in extracorporeal blood circuits (hemoperfusion).

The study demonstrates that different individuals (monkeys) need different heparin doses so as to avoid either clotting or bleeding when an extracorporeal blood system is involved. The linear correlation between PT and WBPTT values enables to utilize the latter for monitoring the heparin level in the blood. One procedure is based on the application of the Gotch and Keen intravenous heparinization model in its steady state limit by utilizing the pre-treatment evaluation of k/S, the ratio of the elimination rate constant to the individual's sensitivity to heparin. A second procedure involves the direct heparinization of the extracorporeal system. The heparin infusion rate is monitored through the arterial WBPTT values after relating the individual's PT or WBPTT values to the in vitro heparin concentration in the blood. In vitro and in vivo study of the effect of hemoperfusion through a column containing anion exchange particles on the amount and rate of heparin administration indicates that only the in vivo results are meaningful. The sharp response of WBPTT to relatively small changes of citrate concentration in the blood precludes individual monitoring by WBPTT. Work on the advantage of utilizing heparin together with citrate is required.

Animals↗

Preparation of a biocompatible albumin-coated ion exchange resin for bilirubin removal from the blood of jaundiced newborns.

Removal of bilirubin by hemoperfusion with ion exchange resin particles is suggested to replace exchange transfusion of blood of jaundiced infants in some cases of unconjugated hyperbilirubinemia. The hemoperfusion system developed here consists of a packed bed of a macroreticular resin which is made biocompatible by a coating of a monomolecular layer of albumin. The choice of the appropriate ionic form of the resin and the proper albumin coating and crosslinking procedure assures a high bilirubin adsorption capacity and excellent blood compatibility of the resin. The albumin coated resin removes in vitro 80-90% of the bilirubin initially present in the plasma. The results encourage in vivo clinical studies.

Adsorption↗

Resin hemoperfusion for unconjugated bilirubin removal.

The application of an anionic macroreticular ion exchange resin, coated with a thin cross-linked albumin layer, as a hemoperfusion device for the removal of unconjugated bilirubin from the blood of hyperbilirubinemic newborn babies is reviewed. In vivo hemoperfusion runs with hyperbilirubinemic animal models - either by a choledocho-suprarenal vein shunt or by direct infusion of bilirubin into the vein - showed that a 40-ml resin column can remove some 20 mg bilirubin in 3 h. Hemoperfusion of female 8-14 kg baboons showed no significant effect of the column on blood chemistry and coagulation factors and repeated runs had no ill effects.

Adsorption↗

Bilirubin removal from an hepatic failure patient by resin hemoperfusion.

An hemoperfusion (HP) column, packed with beads of a macroreticular MR ion exchange resin which were made biocompatible by coating with a fine layer of cross-linked human albumin, was applied to the removal of bilirubin (BIL) from a jaundiced 69-year old man with hepatic failure. The column was found most suitable for BIL removal. However, the high volumetric mass transfer coefficient of the unconjugated (UC) BIL indicates that this column could best be used for BIL removal from babies suffering from unconjugated hyperbilirubinemia.

Acute Disease↗

Removal of bilirubin by hemoperfusion with ion exchange resins.

Removal of bilirubin by hemoperfusion with macroporous resins is suggested to replace exchange transfusion of blood from jaundiced infants. Anion exchangers tested for BIL binding rate and the effects of various system parameters, i.e. particle size, temperature, bed volume, fluid flow rate and particle porosity are reported. The dissociation equilibrium constant K of the BIL-ALB (albumin) complex was determined from the equilibrium adsorption isotherms data, at different ALB concentrations. Increasing ALB concentration decreased the BIL adsorption rate. For a given ALB concentration, the ratio of unbound to total BIL was constant and the initial BIL adsorption rate was independent of total BIL concentration.

Adsorption↗

Bilirubin removal from a jaundiced premature infant by resin hemoperfusion.

To summarize the results: Bilirubin removal by hemoperfusion was successfully performed for the first time on a premature infant. The hemoperfusion caused no adverse effects on the clinical state of the infant. The bilirubin removed in 90 min--13 mg--indicates the existence of a large extravascular pool. Hemoperfusion is suggested for bilirubin removal from newborn babies, reducing the need for blood exchange with bank blood.

Adult↗