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PubMed2006

Formation of parallel strips in thin films of polystyrene/poly(vinyl pyrrolidone) blends via spin coating on unpatterned substrates.

Patterns of parallel strips, consisting of alternating polystyrene (PS) and poly(vinyl pyrrolidone) (PVP) regions, were observed in thin films spin cast from a PS/PVP/chloroform solution on unpatterned substrates. The formation of anisotropic patterns, manifested not only in thickness variation but also in composition variation, was found to be driven by Marangoni instability, with the PS and PVP streams flowing toward the preferred regions as the phase separation induced by solvent evaporation proceeded. The initial viscosity of the polymer solution and the thickness of the spin-cast films were lumped into one single parameter to study the phase morphology development at various initial polymer solution concentrations. Interestingly, the ratio of the square of the film thickness to the viscosity, a parameter loosely related to the Marangoni number, was found to reach a maximum value at the concentration where the strip patterns were most well-developed.

Journal Article↗
PubMed2006

One-step synthesis of gold and silver hydrosols using poly(N-vinyl-2-pyrrolidone) as a reducing agent.

Synthesis of gold and silver hydrosols was carried out in a one-step process by reduction of aqueous solutions of metal salts using poly(N-vinyl-2-pyrrolidone) (PVP). Both kinds of metal nanoparticles were obtained without the addition of any other reducing agent, at low temperatures and using water as the synthesis solvent. Shape, size, and optical properties of the particles could be tuned by changing the employed PVP/metal salt ratio. It is proposed that PVP acts as the reducing agent suffering a partial degradation during the nanoparticles synthesis. Two possible mechanisms are proposed to explain the reduction step: direct hydrogen abstraction induced by the metal ion and/or reducing action of macroradicals formed during degradation of the polymer. Initial formation of the macroradicals might be associated with the metal-accelerated decomposition of low amounts of peroxides present in the commercial polymer.

Journal Article↗
PubMed2006

Poly(vinyl pyrrolidone): a dual functional reductant and stabilizer for the facile synthesis of noble metal nanoplates in aqueous solutions.

Poly(vinyl pyrrolidone) (PVP) has been extensively used in the solution-phase synthesis of many types of colloidal particles, where it is mainly considered as a steric stabilizer or capping agent with a major role to protect the product from agglomeration. In a recent study, we discovered that the hydroxyl end groups of PVP could also serve as a very mild reductant for kinetically controlled synthesis of Ag nanoplates with yields as high as 75%. Here we further demonstrate that hydroxyl-terminated PVP is also a well-suited reductant for the aqueous synthesis of circular, triangular, and hexagonal nanoplates made of other noble metals including Pd, Au, and Pt. The reduction kinetics of a metal salt by the hydroxyl end groups of PVP can be maneuvered in at least two different ways to facilitate the evolution of plate morphology: (i) by adjusting the molar ratio of PVP to the salt precursor and (ii) by altering the molecular weight of PVP. Unlike previously reported studies of Ag and Au thin plates, light was found to have a negligible role in the present synthesis.

Journal Article↗
PubMed2001

Novel polymeric micelles based on the amphiphilic diblock copolymer poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide).

PURPOSE: The purpose of this work was to synthesize a new amphiphilic diblock copolymer of poly(N-vinyl-2-pyrrolidone and poly(D,L-lactide) (PVP-b-PDLLA) capable of self-assembling into polymeric micelles with multiple binding sites and high entrapment efficiency. METHODS: The copolymer was synthesized by ring-opening polymerization of D,L-lactide initiated by potassium PVP hydroxylate. It was characterized by gel permeation chromatography, 1H- and 13C-NMR spectroscopy. The ability of the copolymer to self-assemble was demonstrated by dynamic and static light scattering, spectrofluorimetry and 1H-NMR. The hydrophobic model drug indomethacin was incorporated into the polymeric micelles by a dialysis procedure. Results. A series of amphiphilic diblock copolymers based on PVP-b-PDLLA were successfully synthesized. The critical association concentrations in water were low, always below 15 mg/L. Micellar size was generally bimodal with a predominant population between 40 and 100 nm. PVP-b-PDLLA micelles were successfully loaded with the poorly water-soluble drug indomethacin and demonstrated an entrapment efficiency higher than that observed with control poly(ethylene glycol)-b-PDLLA micelles. It was hypothesized that specific interactions with the hydrophilic outer shell could contribute to the increase in drug loading. CONCLUSION: PVP-b-PDLLA micelles appear to exhibit multiple binding sites and thus represent a promising strategy for the delivery of a variety of drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

The X-ray crystal structure of pyrrolidone-carboxylate peptidase from hyperthermophilic archaea Pyrococcus horikoshii.

The crystal structure of pyrrolidone-carboxylate peptidase (PCP) from hyperthermophilic archaea Pyrococcus horikoshii (PhoPCP) has been determined at 1.6-A resolution by X-ray crystallography. PCP belongs to the C15 family of cysteine protease, and specifically removes the amino terminal pyroglutamate residue from a wide range of N-terminal-blocking peptides. The crystal structure is very similar to that of other hyperthermophiles, Pyrococcus furiosus and Thermococcus litoralis, and even that from the mesophile, Bacillus amyloliquefaciens. The inter-subunit disulfide bonds, which have been proposed as one of the thermostabilizing factors of the PCP from such hyperthermophiles, was not present in PhoPCP. The result suggests that the thermostability of PhoPCP may be obtained by the accumulation of many weak factors.

Amino Acid Sequence↗
PubMed2001

Studies on the effect of polyvinyl pyrrolidone on the activity of chlorhexidine mouthrinses: plaque and stain.

BACKGROUND, AIMS: Polyvinyl pyrrolidone (PVP) was shown in vitro to reduce chlorhexidine induced, dietary staining without affecting the uptake of the antiseptic to the test substrate. The aim of these studies in vivo was to determine whether PVP affected plaque and dietary staining by a low concentration chlorhexidine rinse. METHODS: The plaque and stain studies used a double blind, randomised 6, treatment crossover design involving healthy subjects with a high standard of oral hygiene and gingival health. The rinse formulations under test were: (A) aqueous alcohol (placebo control), (B) 0.03% chlorhexidine, (C) 0.06% chlorhexidine, (D) 0.06% chlorhexidine+1.2% PVP, (E) 0.06% chlorhexidine+5% PVP, (F) 0.06% chlorhexidine+10% PVP. In the plaque study, on day 1 of each period, subjects were rendered plaque free and then rinsed with 15 ml of the test rinse for 60 s. No further tooth cleaning was performed and subjects returned 24 h later for plaque scoring by area. In the stain study, on day 1 of each period, the tongue and teeth of each subject were rendered stain free. Subjects then rinsed under supervision for 60 s with 15 ml of the allocated rinse 8 x a day between 09:00 h and 17:00 h for 3 days. Immediately after each rinse with the test formulation, subjects rinsed for 120 s with 15 ml of warm black tea. Subjects were requested to also drink at least 5 cups of tea or coffee per day. On day 4, stain was scored by area and intensity from designated teeth and dorsum of the tongue. Washout periods were at least 7 days in both studies. RESULTS: Plaque areas were greatest with placebo and least with 0.06% chlorhexidine. Plaque scores increased with increasing concentrations of PVP in the 0.06% chlorhexidine rinse and were significantly higher than 0.06% chlorhexidine without PVP rinse. Tooth stain areas were comparable for placebo, 0.03% and 0.06% chlorhexidine rinses, but significantly reduced with the PVP/chlorhexidine rinses compared to the 0.06% chlorhexidine rinse. Tooth stain intensity was significantly increased with 0.06% chlorhexidine rinses compared to placebo and chlorhexidine/PVP rinses. Tongue stain area and intensity were significantly reduced with 5% and 10% PVP/chlorhexidine rinses compared to 0.06% chlorhexidine rinse. CONCLUSION: PVP, at the concentrations tested, reduced the stain propensity of a 0.06% chlorhexidine rinse but at the expense of some loss of plaque inhibition.

Adolescent↗
PubMed2001

The effect of polyvinyl pyrrolidone on the clinical activity of 0.09% and 0.2% chlorhexidine mouthrinses.

BACKGROUND: Previous studies have shown that polyvinyl pyrrolidone (PVP) added to a chlorhexidine rinse reduced extrinsic dental stain but at the expense of a reduction in plaque inhibitory activity. This effect appeared due to a reduction in the effective chlorhexidine dose to levels where dose response studies show plaque inhibition falls off rapidly. The aim of these 2 clinical studies was to determine if PVP could be added to chlorhexidine rinses to maintain efficacy and reduce staining. METHOD: Study 1 involved 42 healthy dentate volunteers and was a blind, randomised, 7 treatment, crossover design balanced for residual effects. The rinses were: 1. 0.09% chlorhexidine to which was added, 2. 1% PVP, 3. 3% PVP, 4. 5% PVP, 5. 7% PVP, 6. Placebo, 7. Essential oil product. Rinses were used 2x on day one of each period after a prophylaxis. Subjects suspended tooth cleaning for 24 h and were then scored for plaque area. Study 2 used the experimental gingivitis model, involved 24 healthy dentate subjects and was a blind, randomised, 3 treatment, crossover design balanced for residual effects. The rinses were 1. 0.2% chlorhexidine, 2. 0.2% chlorhexidine/10% PVP, 3. Placebo. At baseline and the end of each study period subjects were rendered plaque, stain and calculus free, suspended oral hygiene and rinsed 2x per day. Plaque, gingivitis and stain were scored at baseline, 1, 2, and 3 weeks. Calculus was scored at baseline and 3 weeks. RESULTS: Study 1: Buccal plaque scores were significantly lower with all rinses compared to placebo. Also all buccal plaque scores were significantly lower with chlorhexidine and chlorhexidine/PVP rinses compared to the essential oil/phenolic rinse. There were no significant differences between the chlorhexidine rinse and the chlorhexidine/PVP rinses. Analyses for buccal and lingual plaque combined produced, with one exception, the same results for rinse comparisons as for buccal plaque alone. Thus the essential oil/phenolic rinse just failed to reach significance compared to placebo. Study 2: Plaque and gingivitis scores were significantly lower with positive control and test rinses compared to placebo but with no difference between these rinses. Tooth and tongue stain was significantly higher with the positive control and test rinses compared to placebo but not significantly different between these 2 rinses. Calculus scores were not significantly different between the three study rinses. CONCLUSION: Taken with previous data, the balance of evidence does not support PVP as an inhibitor of staining associated with chlorhexidine. These data are further evidence that chlorhexidine oral hygiene products, which, do not or claim not to cause staining, are most probably lacking efficacy.

Adult↗
PubMed1999

Effects of glycine or (+/-)-3-amino-1-hydroxy-2-pyrrolidone microinjections along the rostrocaudal axis of the dorsal periaqueductal gray matter on rats' performance in the elevated plus-maze task.

The effects of glycine (GLY) or (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA966), a GLY receptor antagonist, microinjections into sites along the rostrocaudal axis of the dorsal periaqueductal gray matter (dPAG) were studied in rats placed on the elevated plus maze (EPM). Selective alterations in the open-arm entries (OAEs) or open-arm time (OAT) of the EPM were the indexes of anxiety. HA966 (30 or 100 nmol, 0.3 microl) increased OAEs and OAT in all 3 dPAG sites, suggesting an anxiolytic effect. GLY (80 and 120 nmol, 0.3 microl) selectively reduced OAEs and OAT, suggesting an anxiogenic effect only when injections were given within the caudal dPAG. When administered together, HA966 reversed the anxiogenic effect of 120 nmol GLY, indicating pharmacological selectivity for the effects of GLY on GLY receptors. Results reinforce an involvement of N-Methyl-D-aspartate-coupled GLY receptors in anxiety and suggest that saturation of this receptor may vary along the dPAG.

Animals↗
PubMed1983

Immunological consequences of intestinal helminth infections in C57BL mice. Humoral responses to polyvinyl pyrrolidone.

Infection with Trichuris muris eggs or Nematospiroides dubius larvae (orally administered) did not affect IgG or IgM antibody responses to 0 X 2 micrograms polyvinyl pyrrolidone (PVP) (intravenously (i.v.) or intraperitoneally (i.p.)) or 20 micrograms PVP (i.p.) in C57BL mice. However, Nippostrongylus brasiliensis L3 subcutaneously (s.c.) and N. dubius L3 (i.v.) significantly increased responses to PVP (i.p.) so migrating larvae are probably responsible. Similar enhancement was obtained when extracts of N. brasiliensis worms or N. dubius larvae were administered i.p. The activity of N. brasiliensis extract was trypsin-insensitive and unaffected by heat (1 h, 60 degrees). Extracts of A. suum did not cause significant enhancement and BALB/c mice were not affected by N. brasiliensis extract. The possible roles of regulatory T-cells, non-specific mitogenesis and macrophage activation are discussed.

Animals↗
PubMed2003

Preparation of silver nanoprisms using poly(N-vinyl-2-pyrrolidone) as a colloid-stabilizing agent and the effect of silver nanoparticles on the photophysical properties of cationic dyes.

The synthesis of silver nanoprisms in aqueous solution using poly(N-vinyl-2-pyrrolidone) (PVP) with different molecular weights (29, 55 and 1300 kg mol(-1)) as a stabilizing agent is described. Low molecular weight PVP (55 kg mol(-1)) is indicated for the preparation of a stable blue solution containing Ag nanoprisms via extended irradiation of a yellow colloidal solution of nanospheres with polychromatic visible light. The fluorescence properties of some cationic dyes (acridine, 9-aminoacridine, Nile Blue and auramine), free and bound to poly(methacrylic acid), have been studied in the presence of different shaped Ag colloidal particles in solution. Only auramine displays an amplification of the fluorescence signal with increasing colloid concentration, while the fluorescence of the other dyes is quenched by interaction with the polymer-stabilized metal nanoparticles.

Journal Article↗
PubMed2006

Spectroscopic characterization and photobleaching kinetics of hypericin-N-methyl pyrrolidone formulations.

Hypericin (HY) is a promising photosensitizer in photodynamic therapy (PDT). It was recently reported that appropriate use of N-methyl pyrrolidone (NMP) enhanced in vivo PDT efficacy of HY and enhanced in vivo delivery of HY. This present study further investigates the use of NMP and other known non-toxic pharmaceutical additives, polyvinylpyrrolidone (PVP, K29/32) and copolyvidonum (S630), for formulating HY to enhance its delivery with photodynamic activity as a goal in mind. Hence, the first objective of this study was to characterize the solubilization of HY by NMP, K29/32 and S630. Thermodynamic considerations were used to explain the solvation process. Photobleaching is another important property of photosensitizers. There is no report on the photostability of HY in pharmaceutical formulations used for PDT. Therefore, the second objective of this study was to investigate the photobleaching of HY in these formulations. The fluorescence of HY was found to increase significantly in higher concentrations of NMP or when 5% of polymer was co-mixed with 5% of NMP solution. The photobleaching of HY in these formulations followed first-order kinetics. The loss of fluorescence paralleled to the loss of absorption of HY. The formulation of HY with 40% NMP was found to be the most stable.

Anthracenes↗
PubMed2001

Thermal stability of pyrrolidone carboxyl peptidases from the hyperthermophilic Archaeon, Pyrococcus furiosus.

The temperature adaptation of pyrrolidone carboxyl peptidase (PCP) from a hyperthermophile, Pyrococcus furiosus (Pf PCP), was characterized in the context of an assembly form of the protein which is a homotetramer at neutral pH. The Pf PCP exhibited maximal catalytic activity at 90-95 degrees C and its activity was higher in the temperature range 30-100 degrees C than its counterpart from the mesophilic Bacillus amyloliquefaciens (BaPCP). Thermal stability was monitored by differential scanning calorimetry (DSC). Two clearly separated peaks appeared on the DSC curves for Pf PCP at alkaline and acidic pH. Using the oxidized Pf PCP and two mutant proteins (Pf C188S and Pf C142/188S), it was found that the peaks on the high and low temperature sides of the DSC curve of Pf PCP were produced by the forms with an intersubunit disulfide bridge between the two subunits and without the bridge, respectively, indicating the stabilization effect of intersubunit disulfide bridges. The denaturation temperature (Td) of Pf PCP with intersubunit disulfide bridges was higher by 53 degrees C at pH 9.0 than that of BaPCP. An analysis of the equilibrium ultracentrifugation patterns showed that the tetrameric Pf C142/188S dissociated into dimers with decreasing pH in the acidic region and became monomer subunits at pH 2.5. The heat denaturation of Pf PCP and its two Cys mutants was highly reversible in the dimeric forms, but completely irreversible in the tetrameric form. The Td of Pf C142/188S decreased as the enzyme became dissociated, but the monomeric form of the protein was still folded at pH 2.5, although BaPCP was completely denatured at acidic pH. These results indicate that subunit interaction plays an important role in stabilizing PCP from P. furiosus in addition to the intrinsic enhanced stability of its monomer.

Adaptation, Physiological↗
PubMed1975

[Pilot study of 2-pyrrolidon-acetamid (generic name: piracetam) (author's transl)].

Ten chronic schizophrenics were tested by clinical observations, psychological tests (FPI, LEV, d 2) and ratings with the Wittenborn-Psychiatric-Ratings-Scales (WPRS) before and after taking 2-pyrrolidon-acetamid. The improvement of obstructive, apathy, withdrawal and affective flatness in seven patients justify a double-blind psychometric evaluation concerning the effect of Piracetam on the schizophrenic deficiency states.

Adult↗
PubMed2003

Serum pyrrolidone carboxypeptidase activity in N-methyl-nitrosourea induced rat breast cancer.

Pyrrolidone carboxypeptidase (Pcp) (E.C. 3.4.19.3) is an omega peptidase widely distributed in animal fluids and tissues and hydrolyses N-terminal pyroglutamic residues from biologically active peptides such as gonadotropin releasing hormone (GnRH). Previous results obtained by us showed a decrease in human breast cancer Pcp activity, suggesting that this enzyme activity or its putative substrates may play a major role in breast cancer pathogenesis. The aim of the present work is to analyse serum Pcp activity in N-methyl-nitrosourea (NMU) induced rat mammary tumours using pyroglutamyl-beta-naphthylamide as substrate. Serum Pcp activity was significantly lower in NMU-treated rats than in controls. Moreover, multiple regression analysis showed a significant correlation between Pcp activity and the number and size of tumours and the body weight of the animals. Since NMU-induced carcinomas are mainly oestrogen-dependent, the decrease observed in Pcp activity may reflect an increase in circulating levels of GnRH that lead to an increase in gonadal steroid hormones production responsible, at least in part, for the initiation and promotion of the disease.

Animals↗
PubMed1971

Enzymatic conversion of 5-oxo-L-proline (L-pyrrolidone carboxylate) to L-glutamate coupled with cleavage of adenosine triphosphate to adenosine diphosphate, a reaction in the -glutamyl cycle.

A new enzyme, 5-oxoprolinase, was found in rat kidney and in several other tissues; it catalyzes the conversion of 5-oxo-L-proline (L-5-oxo-pyrrolidine-2-carboxylic acid, L-2-pyrrolidone-5-carboxylic acid, L-pyroglutamic acid) to L-glutamic acid, with concomitant stoichiometric cleavage of ATP to ADP and orthophosphate. The reaction catalyzed by 5-oxoprolinase, in which 5-oxoproline formed from gamma-glutamyl amino acids by the action of gamma-glutamylcyclotransferase is converted to glutamate, appears to function in the gamma-glutamyl cycle. 5-Oxoprolinase requires Mg(++) (or Mn(++)) and K(+) (or NH(4) (+)) for activity. The equilibrium is markedly in favor of glutamate formation at pH 7.8.

Adenine Nucleotides↗
PubMed1995

Formation of complexes between polyvinyl pyrrolidones or polyethylene glycols and tannins, and their implication in gas production and true digestibility in in vitro techniques.

Various tannin-complexing agents have been used to study the potential adverse effects of tannins on rumen metabolism. Using a method based on turbidity formation, the binding of various tannin-complexing agents (polyvinyl polypyrrolidone (PVPP), polyethylene glycol (PEG) of molecular weights 2000 to 35,000, and polyvinyl pyrrolidone (PVP) of molecular weight 10,000, 40,000 and 360,000) to tannins (tannic acid, purified tannins from quebracho (Aspidosperma quebracho) and leaves of trees and shrubs (Acioa barteri, Dichostachys cinerea, Guiera senegalensis, Piliostigma reticulatum)) was investigated at different pH values. The binding of all the tannins with PVPP was highest at pH 3-4 and lowest at pH 7. For all the pH range (3-7) studied, the binding of PEG was higher than that of PVP. For all the tannins except tannic acid, the binding to PVP was the same from pH 4.7 to 7. Similar results were observed for the PEG of molecular weight 6000 or higher for all the tannins except quebracho tannins for which the binding increased as the pH increased from 3 to 7. The binding with PEG 2000 decreased to a greater extent as the pH reached near neutral and for PEG 4000 this decrease was slightly lower. Addition of these tannin-complexing agents to the in vitro gas system resulted in higher gas production from tannin-rich feeds (increase varied from 0 to 135%). The PEG were the most effective followed by PVP and PVPP. The PEG 35,000 was least effective. The efficiency of other PEG was similar. The PEG 6000 was preferred to PEG 2000 or 4000 as its binding to tannins was higher at near neutral pH values. The gas production increased with an increase in the amount of PEG 6000 up to 0.6 g/40 ml rumen-fluid-containing medium containing 0.5 g tannin-rich feed, beyond which no increase was observed. The percentage increase in gas value at 24 h fermentation correlated significantly with tannin values, the highest correlation (r 0.95) being with protein precipitation capacity of tannins. The increase in gas production was associated with higher production of short-chain fatty acids with little change in their molar proportions, suggesting an increase in organic matter digestibility by inclusion of the PEG in tannin-rich feeds. However, apparent and true digestibilities were lower on addition of the PEG, due to the presence of PEG-tannin complexes in the residues. The use of this bioassay (percentage increase in gas production in the presence of PEG 6000) along with other tannin assays would provide a better insight into the nutritional significance of tannins.

Animals↗
PubMed1998

Pyrrolidone carboxyl peptidase from the hyperthermophilic Archaeon Pyrococcus furiosus: cloning and overexpression in Escherichia coli of the gene, and its application to protein sequence analysis.

A gene for a pyrrolidone carboxyl peptidase (Pcp: EC 3.4.19.3, pyroglutamyl peptidase), which removes amino-terminal pyroglutamyl residues from peptides and proteins, has been cloned from the hyperthermophilic Archaeon Pyrococcus furiosus using its cosmid protein library, sequenced, and expressed in Escherichia coli. The DNA sequence encodes a protein containing 208 amino acid residues with methionine at the N-terminus. Analysis of the recombinant protein expressed in E. coli, including amino acid sequence analysis from the N-terminus by automated Edman degradation and ionspray mass spectrometric analysis of the peptides generated by enzymatic digestions with lysylendopeptidase and Staphylococcus aureus V8 protease, showed its primary structure to be completely identical with that deduced from its cDNA sequence. Comparison of the amino acid sequence of P. furiosus Pcp (P.f.Pcp) with those of bacterial Pcps revealed that a high degree of sequence identity (more than 40%) and conservation of the amino acid residues comprising the catalytic triad, Cys142, His166, and Glu79. On the other hand, a unique short stretch sequence (positions around 175-185) that is absent in bacterial Pcps was found in P.f.Pcp. A similar stretch has also been reported recently in the amino acid sequence of Pcp from the hyperthermophilic Archaeon Thermococcus litoralis [Littlechild et al., in abstracts of the "International Congress on Exthermophiles '98" p. 58 (1998)]. To elucidate their contribution to the hyperthermostability of these enzymes, further structural studies are required.

Amino Acid Sequence↗
PubMed2003

Embolized crospovidone (poly[N-vinyl-2-pyrrolidone]) in the lungs of intravenous drug users.

Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.

Adult↗