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This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: 14C-urea, 3H-mannose, 3H-inulin, and 125I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it is not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier is greater than that of the capillary barrier.

Pinocytic uptake of 125I-labeled bovine serum albumin by 17.5-day rat visceral yolk sac cultured in vitro has been examined. Uptake was followed by intracellular digestion and, after an initial period, the content of radioactivity in the tissue itself remained constant during the incubation. Radiolabel was returned to the culture medium predominantly as (125I)iodotyrosine; exocytosis of undigested protein did not occur. The rate of uptake of labeled protein, which was constant within an experiment and reproducible between experiments, was much higher than that of a nondigestible macromolecule, 125I-labeled polyvinylpyrrolidone. The higher rate of uptake was a consequence of the protein entering the cells chiefly by adsorption to the plasma membrane being internalized; 125I-labeled albumin did not stimualte, nor did 125I-labeled polyvinylpyrrolidone inhibit pinocytosis. Different preparations of 125I-labeled albumin had characteristically different rates of uptake, probably reflecting differences in affinity for plasma membrane receptors. The physiological significance of the findings is discussed.

Several pharmaceutics on the market contain polyvinylpyrrolidone (PVP). As the high-polymeric parts of the PVP molecules cannot be eliminated after parenteral or subcutaneous application, they accumulate in the organism. PVP residues in the dermis cause a considerable variability of skin changes, ranging from deposits nearly without reactions up to swelling, papules, granulomas and pseudotumors.

Synthetic polycations cause a stimulation in the rate of tissue accumulation of colloidal 198Au by the rat visceral yolk sac (at 17.5 days of gestation) and rat peritoneal macrophages cultured in vitro. The mechanism of stimulation has been elucidated in these two cell types by using a dual-substrate technique, and by examining the differential effects of poly(D-lysine) and poly(L-lysine) and of metabolic and cytoskeletal inhibitors. Polycations cause aggregation of colloidal 198Au in the culture medium and increase its affinity for the plasma membrane. In the rat peritoneal macrophage this polycation-colloidal gold complex is pinocytosed, thus enhancing the intracellular accumulation of the radio-labelled substrate. In contrast, the rat visceral yolk sac cannot internalize this complex, and so the substrate accumulates extracellularly. This mechanism of polycation modification affords the opportunity for differential uptake of a substrate into distinct cell types.

Pinocytic capture of 125I-labelled polyvinylpyrrolidone and of formaldehyde-denatured 125I-labelled bovine serum albumin by 17.5-day rat visceral yolk sacs incubated in vitro was rapidly and strongly inhibited by low concentrations (0.01 and 0.05%, v/v) of ethanol. The induced inhibition of pinocytosis was readily reversible, but a marked lag was observed before ethanol-exposed tissue regained its full proteolytic capacity towards the exogenous protein. These observations suggest that the acute administration of ethanol to a pregnant rat may give rise to concentrations of ethanol in the maternal blood and/or uterine fluid that induce dysfunction of the yolk sac. In late gestation such inhibition of yolk-sac function may interfere with the transfer of passive immunity across the yolk sac. If similar dysfunction is induced earlier in gestation, in the period before the chorioallantoic placenta is functional, this could cause a transient period of inhibition of histiotrophic nutrition that may be important to the pathogenic mechanism of action of ethanol as a teratogen.

In the nonanesthetized rat, the jejunal permeability to four simultaneously administered molecules, mannitol, phenol red, inulin and PVP, was measured by analyzing blood, serum, urine and duodenal fluid for these compounds. Of the molecules which had entered the body, approximately 50% were found in the urine, another 50% in the extracellular space and only about 1% were excreted into the duodenal juice. The intracellular content of the molecules is not accounted for in these numbers. The rate of permeation decreased with increasing molecular weight of the substances. EDTA (25 mmol/l) and deoxycholate (5 mmol/l) increased the jejunal permeability for these molecules but not for mannitol. The alterations in mucosal cell turnover and morphology induced by hydroxyurea did not change jejunal permeability for mannitol and phenol red at any time. 24 and 48 h following hydroxyurea, jejunal permeability for inulin and PVP was decreased.

Cardiac pacing leads coated with povidone-[131I] were implanted in dogs and the leaching of radioactivity from the leads was monitored by external scintigraphy. The activity which had dissipated from the pacing leads was not as [131I]-iodide, but as povidone-[131I]. Only 50% (mean) of the activity remained on the pacing leads after two weeks while a significant amount of radioactivity was eliminated via urine and feces. The liver was a major site of accumulation of retained activity which had leached off the pacing leads. There was no evidence of large pieces of povidone-[131I] in the lungs of the dogs, all of which appeared healthy at the time of sacrifice. The results of this study support the conclusions of a long-term study indicating that povidone is a safe and suitable coating material for pacing leads.

The parenteral use of polyvinylpyrrolidone (PVP) leads to PVP retention in the human organism. Four case histories dealing with patients on long-term treatment with a PVP-containing vasopressin preparation are presented and the possibility of a harmful effect of the PVP storage is discussed. The presence of PVP in serum, demonstrated by lipoprotein electrophoresis, is described. Based on the literature and the present findings, a withdrawal of PVP-containing preparations for injectional purposes is advocated.

A method is described for the in vitro culture of 17.5-day rat visceral yolk sac. Tissue survival was good as judged by light and electron microscopy. The rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone by the tissue was constant both within and between experiments. Within the concentration range 0.15-24 mug/ml, the 125I-labeled polyvinylpyrrolidone neither stimulated nor inhibited pinocytosis. The system offers many advantages in the quantitative study of the physical basis of pinocytosis.

Lysosomotropic agents--Triton WR 1339 and suramin--are taken up selectively into lysosomes during in vivo administration and cause specific changes of the particles. Overloading of rat liver lysosomes by Triton WR 1339 was accompanied by the labilization of lysosomes and an increased uptake of [14C]-bovine serum albumin ([14C]-BSA) by the rat liver. The rate of intralysosomal proteolysis was not altered. The capture of 125I-labelled poly(vinylpyrrolidone) (PVP) by the liver was slightly decreased. In the case of suramin administration (250 mg/kg b.w.) the uptake of labelled protein by the liver was not changed. The increased amount of acid-insoluble radioactivity in rat liver was caused by the decrease of intralysosomal protein digestion rate. The lysosomes overloaded by the two kinds of lysosomotropic agents--Triton WR 1339 (with no changes of intralysosomal proteolysis) and suramin (with decreased rate of proteolysis) did not prevent the uptake by liver of substances captured by the adsorptive ([14C]-BSA) or fluid ([125I]-PVP) endocytosis.

Permeability of the small intestinal mucosa was estimated using a perfusion technique after either a period of ischaemia or exposure to acetyl salicylate. It was shown that these procedures increased the passive permeability of the mucosa to macromolecules while maintaining normal mucosal selectivity. Histologically, there was derangment of the epithelial cell layer of the villous tips without damage to the epithelial basement membrane or subepithelial structures. It is concluded that the epithelial cell layer is purely limiting with no selective function and that the role of selectivity must be ascribed to either or both of the other mucosal barriers, the capillary and the epithelial basement membrane.

The uptake of free and liposome-entrapped 125I-labelled poly(vinylpyrrolidone) was measured in an intestinal sac preparation from adult rats. At an equal concentration of 125I-labelled poly(vinylpyrrolidone), the rate of uptake of the liposome-entrapped material was four times that of the free macromolecule.

Biopsy specimens of lymph nodes or bone marrow taken from two cases, which seemed to have received intravenous infusions of polyvinylpyrrolidone (PVP) more than 15 years ago, were examined histopathologically, histochemically or electron microscopically. In the lymph nodes, proliferation of foam cells, often with multinuclear giant cells, and basophilic vacuolar massive deposition were found markedly in the lymphatic sinuses and sporadically in the parenchyma. In the bone marrow, basophilic foam cells predominated, together with infrequent appearance of multinuclear giant cells and basophilic vacuolar deposits. The basophilic materials stored in the foam cells and multinuclear giant cells, as well as basophilic vacuolar massive deposits, were histochemically proved to stain with the special stains for demonstration of PVP. Electron microscopically, storage inclusions observed in the cytoplasm of PVP-storing macrophages were comprised of electrondense, amorphous substances or of vacuolar, fine reticulogranular, flocculent materials and were bounded by a single delimitating membrane. Most of the inclusions, particularly osmiophilic ones, showed intense acid phosphatase activity, while larger, vacuolar inclusions had a reduced or no enzyme activity. Extracellularly, vacuolar storage inclusions with no enzyme activity were found. The possible mechanism of long-term PVP storage in the tissues was briefly discussed.

The translocation of Percoll microspheres (mean diameter 20-30 nm) from the intestinal lumen through the epithelial layer to internal organs was examined in suckling mice using transmission electron microscopy. Repeated administration of this material by gavaging for 7 consecutive days resulted in a heavy particle load of vacuolated enterocytes. A limited amount of Percoll was transported to the subepithelial tissue of both the villous mucosa and Peyer's patches where microspheres were found endocytosed, predominantly by macrophages. Even smaller numbers of particles reached mesenteric lymph nodes and, occasionally, milky spots of the omentum. Minor Percoll aggregates were easily found in Kupffer cells of the liver, indicating hematogenous translocation. Small numbers of particles were regularly detected in perivascular macrophages of the thymic cortex, which are in close contact with surrounding lymphocytes. We conclude that the thymic cortex is not totally inaccessible to particulate matter of the intestinal content.

Equilibrium dialyses and fluorescent spectroscopic measurements demonstrated that human serum albumin (HSA) affects the oxytetracycline (OTC)--polyvinyl-pyrrolidone K 90 (PVP) interactions. The preferential binding of OTC with HSA, as compared to PVP, was evidenced by means of a three-compartment model. The binding values increased with the increase of the portion of PVP in the PVP-HSA mixture. Superadditive OTC bindings occurred at a ratio of 1:1 (by weight). The addition of Mg2+ to PVP-containing solutions, at a molar ratio of 1:1, also produced an increase of the interactions of this antibiotic with PVP, whereby maximal OTC-PVP bindings of 50--60% were reached.

Day 17.5 yolk sacs from rats injected with partially denatured 125I-labeled bovine serum albumin (I-BSA) were cultured in vitro by a raft technique. The rates of release of [125I]iodotyrosine were similar in control yolk sacs and in yolk sacs from rats preinjected with trypan blue. Day 17.5 rat yolk sacs were also cultured in medium containing I-BSA. Following pinocytic uptake the substrate was degraded intracellularly and [135I]iodotyrosine released into the medium. Trypan blue, when present in the medium in concentrations above 100 mug/ml, inhibited pinocytosis of I-BSA and so decreased the rate of [125I]iodotyrosine production. Trypan blue similarly decreased the rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone. Pinocytic uptake of macromolecules was not decreased in yolk sacs from rats pretreated with trypan blue. The relevance of these results to the mechanism of teratogenic action of trypan blue is discussed. It is proposed that if trypan blue in teratogenic doses similarly inhibits pinocytosis by the yolk sac during the organogenetic period teratogenesis might result from a transient interruption in the flow of metabolites through the yolk sac to the embryo.

The small intestinal exudates of patients with protein-losing enteropathies produced by celiac disease or proximal jejunal Crohn's disease were compared with controls. The exudates in control subjects were highly selective, whereas those of the celiac and Crohn's disease subjects were relatively nonselective. It is believed that this loss of selectivity is secondary to basement membrane damage. An analogy is drawn with the renal lesion in nephrotic syndrome where basement membrane damage is associated with nonselective proteinuria.

When added to the serum-free medium in which 17.5-day rat yolk sacs were incubated, formaldehyde-denatured 125I-labelled bovine serum albumin was rapidly degraded. More than 80% of the radiolabelled digestion products appearing in the incubation medium consisted of [125I]iodo-L-tyrosine; larger digestion products were found only in association with the yolk-sac tissue. In the early stages of an incubation, low-molecular-weight digestion products began to appear in the incubation medium only after they could be detected within the tissue, and progressive association of trichloroacetic acid-insoluble radioactivity with the tissue preceded both these events. None of the observed proteolysis could be attributed to proteinases released into the incubation medium. Tissue-associated acid-insoluble radioactivity showed a lysosomal distribution on sub-cellular fractionation, and cell-free homogenates of yolk sacs degraded albumin only at acid pH values. Progressively decreasing the rat of pinosome formation (either by progressively lowering the incubation temperature or by the use of increasing concentrations of the metabolic inhibitor rotenone) caused a corresponding decrease in the rate of degradation of albumin. These findings indicate that, in vitro, formaldehyde-denatured 125I-labelled bovine serum albumin is digested by rat yolk sacs exclusively intracellularly, within lysosomes.

We adapted a method for dialyzable calcium from fluorometric detection by use of calcein to a more specific spectrophotometric determination with cresolphthalein complexone. The reagents are available commercially and perform satisfactorily with respect to noise level, drift, stability, and sensitivity. Construction of the continuous-flow manifold with commercially available components (injection blocks, coils, and dialyzer) and the use of a 9-mm pathlength flow cell in an AutoAnalyzer I colorimeter have permitted a sampling rate of 70/h, and decreased the volume of serum required to 130 microL. A comparison of 71 sera analyzed by the present and the calcein method gave means of 1.39 (SD 0.14) and 1.39 (SD 0.13) mmol/L, respectively. The regression equation was: present method = 1.016 calcein--0.022 mmol/L (r = 0.97). The CV for the new method, as determined from 46 randomized duplicate analyses, was < 1%. The reference interval, as evaluated from results for 93 different individuals, was 1.26-1.43 mmol/L. We conclude that our methods is an improvement with respect to noise level, drift, specificity, detectability, and more general availability of instrumentation. Moreover, the smaller sample volume required makes possible the routine measurement of dialyzable calcium in pediatric samples.

Radiolabelled compounds of different molecular size were used as tracers mixed with seminal plasma to investigate whether seminal plasma enters the oviducts of inseminated gilts. The substances were 125I-labelled human serum albumin for 3 gilts, 131I-labelled polyvinylpyrrolidone plus 59Fe citrate in 2 gilts and 131I-labelled human serum albumin plus 59Fe citrate in 2 gilts. The gilts were slaughtered 1 h after insemination and the radioactivity was measured in 4 parts of the oviduct, 9 parts of the uterine horns, the body of the uterus and the cervix. Different quantities of the compounds used were found in all oviducts, but there was close agreement between the distributions of the two compounds in the genital tract after simultaneous insemination. There was a difference (60-80%) in total amount of recovered radioactivity between left and right uterine horns. It is concluded that all compounds used entered the oviducts regardless of their molecular sizes.

If liposomes are to be effective as carriers for the oral administration of insulin they must be able to withstand passage through the stomach and small intestine. Multilamellar liposomes, some identical in composition to those used in reported in vivo studies on the uptake of orally administered insulin, were tested in vitro for their stability in the presence of bile salts, pancreatic lipase, and variations in pH. While low or high pH had little effect on most liposomes, 10 mM bile salts caused the release of over 80% of entrapped marker from all liposomes tested except those composed of distearoyl phosphatidylcholine/cholesterol and those composed of dipalmitoyl phosphatidylethanolamine/cholesterol/dicetylphosphate. However, the latter were unstable at low pH. The distearoyl phosphatidylcholine/cholesterol liposomes were also resistant to pancreatic lipase, and therefore may be suitable for use in the oral administration of therapeutic agents.

Conceptuses from 9.5-day pregnant rats were cultured for 48 h in heat-inactivated homologous serum to which leupeptin, a specific inhibitor of the lysosomal cysteine-proteinases, was added for the final or the penultimate 6 h. The presence of leupeptin (25 micrograms/ml or above) increased the protein content of yolk sacs at harvesting to approximately twice the control value. The protein content of the embryo at harvesting was lower than that of controls. When 125I-labelled polyvinylpyrrolidone was added to the culture serum for the final 6 h of culture, radioactivity was found in the yolk sac at harvesting, but not in the embryo. The presence of leupeptin did not affect the rate of uptake of the radiolabelled macromolecule by the yolk sac, nor facilitate its entry into the embryo. When formaldehyde-denatured 125I-labelled bovine serum albumin was added to the culture medium for the final 6 h of culture, little radioactivity was found in the yolk sac at harvesting, and barely any was found in the embryo. Trichloroacetic acid-soluble radioactivity was found in the culture serum. The presence of leupeptin sharply increased the levels of radioactivity in the yolk sac (but not the embryo) and sharply decreased the acid-soluble radioactivity of the culture medium. When rat serum whose proteins were labelled with [3H]leucine was used as culture medium, radioactivity was found in both yolk sac and embryo at harvesting. The presence of leupeptin increased the amount found in the yolk sac and decreased that found in the embryo. These results are interpreted as follows. Leupeptin enters the lysosomes of the yolk sac, inhibiting their cysteine proteinases. The digestion of proteins pinocytosed by the yolk sac is consequently inhibited, resulting in the accumulation of protein by the yolk sac and a decreased flow of amino acids to the embryo. Leupeptin (50 mg/kg), injected into pregnant rats at either 8.5 days or 9.5 days of gestation, induced congenital malformation in the offspring. It is proposed that leupeptin exerts its teratogenic action by inhibiting proteolysis in the lysosomes of the yolk sac, and so depriving the developing embryo of its supply of amino acids at a critical stage of development.

A man, aged 67, has been treated in 1968 by X-rays for a basal-cell carcinoma of the back. The treatment was followed by an ulcerative radiodermatitis. 3 years later, the patient was treated by ten intramuscular injections of procaine-polyvinylpyrrolidone (or procaine-povidone) for sciatic neuralgia. An orange infiltration appeared progressively around the radiodermatitis. The area was excised in 1979 and polyvinylpyrrolidone (povidone) storage, responsible for the ring-shaped orange hue, could be demonstrated in the dermis and subcutaneous fat. Special stainings confirmed the presumed chemical nature of the deposits. 3 cases of povidone pseudotumours following procaine-povidone injections had been described previously. The preferential deposit of povidone in RX-damaged skin is discussed.

The uptake of free and liposome-entrapped 125I-labelled PVP was measured in and intestinal-sac preparation from adult rats. Uptake of the free macromolecule was directly proportional to the substrate concentration and was reduced by colchicine and sodium azide. Uptake of the liposome-entrapped macromolecule was greater than that of the free macromolecule, was not directly proportional to substrate concentration, showed signs of saturation at high liposome concentrations, and was also reduced by sodium azide and colchicine. These results suggest that gut epithelial cells take up the free macromolecule by fluid-phase endocytosis and the liposome-entrapped macromolecule by adsorptive endocytosis.

The authors report on a case of isolated mandibular localization of polyvinyl-pyrrolidine thesaurismosis. The patient, a man of 38, had been treated with injections of posterior pituitary extract, for a period of eighteen months, 10 year ago. Localization in the mandible is extremely rare, making diagnosis difficult unless a detailed anamnesis is available.

Impaired overall phagocytic function, as measured by clearance of radio-labelled polyvinyl pyrrolidone from the blood (KPVP), has been demonstrated in mice whose dietary intake of the essential amino acids phenylalanine and tryptophan was reduced to less than a quarter of that in a standard diet which supported optimal growth. This was associated with loss in weight of body, liver, spleen and thymus and an increase in the phagocytic index, alphaPVP.

1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed.

The rates of elimination of iodinated human serum albumin (ALBUMIN-125I), polyvinylpyrrolidone (PVP-125I); and tritiated dextran (DEXTRAN - METHOXY-3H) (mol masses of 69 000 - 72 000, 30 000 - 40 000 and 60 000 - 90 000 respectively) from the circulation of sheep were studied; albumin and PVP initially disappeared from the circulation rapidly having half-life times (t 1/2) of 10,5 +/- 3,7 and 43 +/- 45 hours respectively. This phase is regarded as being due to equilibration within the initial volume of distribution, the rate being determined primarily by the relative mol. mass of the molecule. Hereafter PVP-125I was eliminated considerably faster (t 1/2 = 176 +/- 39 h) principally via the kidneys. The limited data available for dextran-3 H suggests that this particular substance is rapidly excreted via the kidneys (t 1/2 = 9 h).

A 58-year-old man had a persistent perineal sinus following an abdominoperineal resection. An excision of the sinus was performed. Histology revealed that the sinus tract was bordered by a granulation tissue exhibiting numerous vacuolated cells containing polyvinylpyrrolidone. The origin of polyvinylpyrrolidone was related to lengthy irrigation of the fistula with Betadine.

Rat peritoneal macrophages in vitro capture 125I-labelled polyvinylpyrrolidone entrapped within either negatively or positively charged liposomes more rapidly than they do the free macromolecule. The uptake of negatively charged liposomes was linear with time over 10 h, whilst the uptake of positively charged ones, although more rapid, was more transient. Neither type of liposome was taken up in the presence of 2,4-dinitrophenol (100 microgram/ml), and 5 mM calcium chloride increased the uptake of negatively charged liposomes. The enhanced uptake of 125I-labelled polyvinylpyrrolidone when presented in liposomes must have been a consequence of entrapment rather than of a simple interaction between lipid and polyvinylpyrrolidone since the presence of the lipids employed or of empty liposomes had no effect on the uptake of unentrapped 125I-labelled polyvinylpyrrolidone.

The sieving characteristics of the normal and inflamed rectal mucosa are studied in three healthy volunteers and five patients with ulcerative colitis. Following rectal instillation of (125)I-polyvinylpyrrolidone (PVP), the molecular size distribution of labelled PVP in urine samples was determined by Sephadex gel filtration. The results of the study suggest that the increased permeability of the inflamed rectal mucosa to electrolytes and small hydrophilic compounds is due primarily to ultrastructural changes since only the low molecular fractions of PVP were found in the urine.

An increase in the concentration of serum resulted in a very marked increase in the rate of fluid-phase pinocytosis in rat peritoneal macrophages, as measured by the uptake of 125I-labelled polyvinylpyrrolidone. In contrast, the rate of uptake of colloidal [198Au]gold, an adsorptive substrate, decreased when the serum concentration was increased. This lessened uptake of colloidal gold must be due to competition by serum components. Studies on the specificity of pinocytosis of simple proteins, using 125I-labelled H4 and M4 forms of porcine lactate dehydrogenase, and formaldehyde-denatured and untreated bovine serum albumin as substrates, suggest that positive charge and hydrophobicity determine adsorptive pinocytosis of simple proteins in peritoneal macrophages. The rate of fluid-phase pinocytosis and the specificity of adsorptive pinocytosis in peritoneal macrophages are very similar to those reported for Kupffer cells.

Three-fold administration of polyvinylpyrrolidone (PVP), molecular weight 24 000, in a dose of 3.3 ml of 0.6% solution per 100 g/bw to rats was accompanied by disorders of lysosomal integrity and increased vulnerability to damage of the particles in the hypotonic medium (as judged from acid ribonuclease and cathepside D release). Five days after a single administration 125I-PVP was retained primarily by liver cells (7.3% of the dose administered) and to a lesser degree by renal cells (0.43%) and spleen cells (0.93%). Ninety per cent of the labeled PVP was bound to granular fractions of the rat liver (pinosomes, heterolysosomes). In the course of particles destruction by 0.1% Triton X-100 90% of 125I-PVP was released into the supernatant, which confirms the lysosomal localization of the compound.

It was shown that Clostridium perfringens epsilon toxin has the effect of allowing the passage of 125I polyvinyl-pyrrolidone and 125I human serum albumin into mouse brain. These substances did not enter the brains of normal control mice. The passage of albumin into the brains of mice poisoned with epsilon toxin was extremely rapid. When large doses of toxin (+/-4 000 MLD) were given death ensued within 2-3 min at which stage 1,5% of the injected albumin had already entered the brain. In cases where smaller doses were given and the time interval between injection and death was longer the figure was increased to 2-2 1/2% of the injected plasma albumin.

A series of experiments was conducted using White Leghorn male chicks to study the arginine-lysine relationship in rapeseed meal (RSM). Semi-purified diets containing 15% protein either from RSM or soybean meal (SBM) were fed. Arginine supplementation completely reversed the growth depression caused by the addition of lysine to RSM diets. Potassium acetate was only partially effective in alleviating the growth depression caused by supplemental lysine, while polyvinyl pyrrolidone significantly reduced chick performance. Tannic acid addition (1.5%) to SBM diets resulted in a severe growth depression which was partially corrected by the supplementation of arginine in the presence of methionine. Supplementation of these amino acids to RSM had a less drastic effect. It is suggested that a portion of the arginine in rapeseed meal may be required for metabolic processes involved in tannic acid excretion.

The tissue distribution and excretion of 14C-labelled povidone (polyvinylpyrrolidone; K-30; average mol wt 40,000) was studied in male Sprague-Dawley rats given a single oral dose. The major pathway of elimination of radioactivity was in the faeces, in which 90.8% of the administered dose was recovered after 12 hr and 98.4% after 48 hr. Amounts of radioactivity in major tissues and in the blood were not significantly different from those in untreated controls. A minor amount of radioactivity, representing 0.04% of the administered dose, was detected in the urine after 6 hr. Dialysis studies of [14C]povidone suggested that the absorbed species was a low-molecular-weight (less than 3500) oligomer. It was concluded that an oral dose of [14C]povidone is not significantly absorbed in the rat.