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PubMed2003

[Soluble adhesion molecules in female patients with breast carcinoma].

BACKGROUND: Serum levels of some soluble adhesion molecules (e.g. ICAM-1, or E-selectin) are higher in some patients with breast cancer (especially metastatic) compared to controls. They bring about the increased risk of developing metastases and they can negatively influence the prognosis of patients. The aim of our study was to assess the serum levels of several soluble adhesion molecules (soluble E-selectin, P-selectin, ICAM-1, VCAM-1 and CD44s) in patients with breast cancer in clinical stage 0-IV before the beginning of hormonal therapy and/or chemotherapy. We wanted to find out if these parameters differ between various stages of breast cancer and if their levels are influenced by the therapy. METHODS AND RESULTS: We examined 59 mostly postmenopausal patients with breast cancer in clinical stage 0-IV (mean age was 62 years). One patient was in stage 0, 10 patients were in stage I, 24 patients were in stage IIA, 11 patients were in stage IIB, 5 patients were in stage III and 8 patients were in stage IV. Serum levels of soluble E-selectin, P-selectin, ICAM-1, VCAM-1 and standard form of CD44 were assessed using ELISA in sera of patients with breast cancer before the institution of hormonal therapy and/or chemotherapy and 3 and 12 months after the beginning of therapy. Compared to controls, patients with (metastatic and also non-metastatic) breast cancer before the beginning of therapy had higher serum levels of soluble E-selectin, P-selectin, ICAM-1 and standard form of CD44. Serum levels of E-selectin, ICAM-1 and also VCAM-1 significantly decreased one year after the beginning of therapy. Serum levels of soluble adhesion molecules mutually correlated and they also correlated with serum levels of soluble TNF and IL-2 receptors and some acute phase proteins (CRP and orosomucoid). CONCLUSIONS: Serum levels of some soluble adhesion molecules (E-selectin, P-selectin, ICAM-1 and CD44s) were higher in some patients with breast cancer and decreased again after hormonal therapy and/or chemotherapy. Only larger studies with longer follow-up may imply if any of these parameters (e.g. soluble P-selectin), or their combination may become useful marker of activity and/or outcome.

Adult↗

PubMed1990

Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts.

We previously showed that carcinogenic nickel, arsenic, and chromium(VI) compounds induced anchorage independence (AI) in diploid human fibroblastic cells (HFC) derived from foreskins (K. A. Biedermann and J. R. Landolph, Cancer Res., 47: 3815-3823, 1987). To elucidate the role of the valence state of chromium and solubility of chromium compounds in inducing AI, we studied the ability of soluble and insoluble hexavalent [chromium(VI)] and trivalent [chromium(III)] chromium compounds to induce mutation and AI in HFC. Chromium(VI) compounds (PbCrO4, CaCrO4, Na2CrO4, and CrO3) were 1000-fold more cytotoxic to HFC (average 50% lethal dose 0.5 microM) than chromium(III) compounds (CrCl3, Cr2O3, Cr2S3; average 50% lethal dose 500 microM). However, equal concentrations (0.1-10.0 microM) of soluble or insoluble chromium compounds in either +6 or +3 valence states induced similar increases in frequencies of AI in HFC (100-200/10(5]. Chromium(VI)- and chromium(III)-induced AI was a stable phenotype. All soluble chromium(VI) and insoluble chromium(III) compounds studied induced mutation to 6-thioguanine resistance at cytotoxic concentrations in HFC. Insoluble PbCr(VI)O4 and a soluble form of Cr(III)Cl3 were inactive in this assay. Mutation induction by chromium(III) compounds only occurred at cytotoxic concentrations (100-1000 microM) 1000-fold greater than those concentrations of chromium(VI) compounds (0.25-1 microM) which were cytotoxic, mutagenic, and induced AI. Soluble hexavalent Na2(51)CrO4 was taken up facilely by cells at concentrations that induced cytotoxicity, mutation, and AI. At concentrations of 0.25-1.0 microM, which induced AI but were not cytotoxic or mutagenic, or concentrations of 1-1000 microM, which were cytotoxic and mutagenic, soluble trivalent 51CrCl3 was not taken up by cells. An insoluble form of CrCl3 was not taken up intracellularly but did avidly associate with cells over the concentration range 1 to 100 microM which induced AI, cytotoxicity, and mutagenicity. Therefore, both chromium(VI) and chromium(III) compounds induced genotoxic effects in human fibroblasts. Cellular uptake, cytotoxicity, mutagenicity, and AI induced by soluble chromium(VI) compounds all occurred at the low concentrations of 0.2 to 1.0 microM; hence mutagenicity and induction of AI may be coupled for soluble chromium(VI) compounds but not for insoluble PbCrO4, which induced AI but was not mutagenic. Cytotoxicity and mutagenicity of insoluble chromium(III) occurred at concentrations of 10-100 microM, but induction of AI occurred at concentrations of 0.1-10 microM, indicating that inductions of mutagenicity and AI were not coupled for chromium(III) compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗

PubMed1987

Interaction of cytoplasmic tyrosine hydroxylase with chromaffin granule. In vitro studies on association of soluble enzyme with granule membranes and alteration in enzyme activity.

The interaction of soluble tyrosine hydroxylase with isolated chromaffin granule membranes was studied. The incubation of the granule membranes with the soluble fraction in the mixture that may approximate the intracellular environment of the resting cell resulted in a marked increase in the enzyme activity recovered in the membrane fraction, and enzyme activity precipitated with the granule membranes was increased according to incubation time and dependent on amounts of both the granule membranes and soluble fraction. The association of the soluble enzyme with the granule membranes was reversible and specific, whereas a decrease in activity of the soluble enzyme was observed when the soluble fraction was incubated with the granule membranes in the mixture in which association of the soluble enzyme with the granule membranes might occur. These results seem to indicate that activity of the soluble enzyme is presumably modulated by the granule through association of the soluble enzyme with the surface of the granule, thus suggesting that interaction between tyrosine hydroxylase and the chromaffin granule may play a possible role in regulation of catecholamine biosynthesis as a consequence of modulating activity of the rate-limiting enzyme within the cell.

Adrenal Medulla↗

PubMed1988

Soluble and Lente human insulin mixtures in normal man.

The interaction between soluble (Actrapid HM) and Lente (Monotard HM) human insulin preparations was examined in normal subjects. Incremental plasma insulin levels were determined following the subcutaneous administration of 6 U of soluble insulin admixed with 0.14 ml soluble insulin diluting medium, or 0.14 ml Lente diluting medium and injected either immediately or 5 min after preparation. For comparison separate but simultaneous injections of soluble (6 U) and Lente insulin (14 U) were administered subcutaneously. All injection volumes were identical. The incremental insulin levels were significantly greater between 60 and 90 min (p less than 0.05-0.01) following the administration of soluble insulin admixed with its own medium compared to the soluble insulin/Lente medium admixtures injected immediately and 5 min after preparation. There was no difference, however, in the plasma insulin profiles between the two soluble insulin/Lente medium schedules. The separate simultaneous administration of soluble and Lente insulin resulted in significantly higher plasma insulin levels at 30 and 90 min (p less than 0.05) when compared to the admixture injected immediately after preparation and from 30-120 min (p less than 0.05-0.01) compared to the admixture injected after 5 min. The two soluble/Lente insulin admixtures achieved similar plasma insulin profiles. Therefore when soluble human insulin is admixed with Lente human insulin and administered by subcutaneous injection immediately after admixing there is a significant reduction in the plasma insulin levels during the first 90 min in contrast to when the two preparations are given simultaneously by separate injection. Delaying the injection of the admixture for 5 min results in significantly lower insulin levels up to 120 min. These differences are reflected in the hypoglycaemic responses observed.

Adult↗

PubMed1985

Induction of protective immunity against Schistosoma mansoni by a non living vaccine. I. Partial characterization of antigens recognized by antibodies from mice immunized with soluble schistosome extracts.

A single intradermal injection of frozen and thawed schistosomula in conjunction with the bacterial adjuvant Mycobacterium bovis strain Bacille Calmette Guerin, Phipps substrain (BCG) induced significant levels of resistance to challenge Schistosoma mansoni infection in C57BL/6 mice. Immunization with the aqueous fraction remaining after 100,000 X G centrifugation of the larval lysate was also protective under these conditions, suggesting that some immunogenic determinants may not be membrane associated. Frozen-thawed cercariae and soluble components of adult worms also protected against challenge infection in these experiments. These observations indicate that soluble immunogens are present in both early and late developmental stages of the parasite, and therefore may be good candidate antigens for an immunochemically defined vaccine against schistosomiasis. Induction of humoral reactivity against soluble or membrane antigens was examined in mice protected against cercarial challenge by prior exposure to frozen-thawed larvae, soluble larval, or soluble adult antigens plus BCG. Animals that were immunized with frozen-thawed larvae produced low but significant levels of antibodies against larval surface antigens when examined by indirect immunofluorescence or by immunoprecipitation of surface-labeled schistosomula. Mice immunized with soluble antigens, however, showed negligible antibody reactivity against surface membrane antigens. Because mice immunized with soluble antigens were resistant to challenge infection, these results strongly suggest that anti-surface membrane reactivity is not required in the mechanism of protective immunity in this model. Sera from mice immunized with either total freeze-thaw larval lysate or soluble schistosome extracts all showed strong reactivity against soluble antigens, as detected by ELISA. Western blot analysis showed these antisera to react with a restricted number of high m.w. antigens that were present both in schistosomula and in adult worms. These antigens are therefore likely to play a major role in the development of resistance in this model as immunogens and/or as targets of protective immune response.

Adaptation, Physiological↗

PubMed1994

Effectiveness of intrathymic inoculation of soluble antigens in the induction of specific unresponsiveness to rat islet allografts without transient recipient immunosuppression.

Our finding that intrathymic inoculation of resting T cells but not dendritic cells induces donor-specific unresponsiveness to organ allografts led us to hypothesize that presentation of MHC class I alloantigens by thymic antigen-presenting cells to T cell precursors during their ontogeny may convey a tolerogenic signal to the recipient. In this study, we examined whether intrathymic inoculation of soluble antigen obtained from 3M KCl extracts of allogeneic T cells could induce donor-specific unresponsiveness to islet allografts in the Lewis-to-WF rat combination. Our results showed that while intrathymic injection of 0.5 mg soluble antigen on day -7 relative to islet transplantation caused acute graft rejection, intrathymic inoculation of 1.0 mg soluble antigen significantly prolonged the survival of Lewis islet allografts from 10.3 +/- 1.1 days in controls to 53.5 +/- 15.6 days (P < 0.001) in naive (nonimmunosuppressed) STZ (streptozotocin)-induced diabetic WF recipients. In contrast, intrathymic inoculation of 2.0 or 4.0 mg soluble Ag on day -7 led to indefinite Lewis islet survival (> 150 days) in all naive diabetic WF recipients; a finding that suggests that 2.0 mg soluble Ag is the optimal effective dose of intrathymic inoculum required to induce donor-specific unresponsiveness in naive recipients in this model. This finding could not be reproduced by intravenous injection of 2.0 mg soluble Ag, thus confirming the privileged position of the thymus in the induction of Ag-specific unresponsiveness. Third-party (BN) islet allografts were rejected in an acute fashion in similarly prepared recipients. Our results suggest that (1) intrathymic inoculation of soluble Ag, unlike cellular Ag, induces donor-specific unresponsiveness to islet allografts without the use of transient recipient immunosuppression; (2) induction of specific unresponsiveness appears to be dose dependent; and (3) the tolerogenic effect of soluble Ag is dependent on the indirect pathway of Ag-presentation in the thymus in the absence of donor antigen-presenting cells in the inoculum. This novel approach of thymic reeducation of adult animals by the deliberate intrathymic inoculation of soluble major histocompatibility complex Ag without the use of recipient immunosuppression may have therapeutic potential in the induction of transplantation tolerance.

Animals↗

PubMedDate not supplied

Increased serum levels of soluble tumor necrosis factor a-receptors in patients undergoing partial liver resection.

BACKGROUND/AIMS: This study was conducted to evaluate the association of tumor necrosis factor-a and soluble receptors as known antagonists in liver surgery with regard to ischemia and reperfusion. METHODOLOGY: Preoperative and perioperative changes of TNF, soluble TNF receptor I and II as well as IL-6 were evaluated in twelve patients with partial liver resection. Before liver ischemia and after reperfusion, the levels were measured in the portal and hepatic vein, as well as systemically. Ten patients with gastrectomy and lymphadenectomy as another major abdominal operation and eight healthy volunteers served as the control groups. RESULTS: Uncomplicated liver resections were associated with a prolonged and significantly increased release of soluble receptors until the third (for soluble receptor I) or the fifth postoperative day (for soluble receptor II). No tumor necrosis factor immunoreactivity could be detected, except in one patient with postoperative sepsis. The pattern of interleukin-6 immunoreactivity during liver resection was characterized by a delayed peak on day 2 (p<0.01 vs preop), compared to an early peak after 8 hours in control patients undergoing gastrectomy (p<0.05 vs preop). Liver resection elicits a release of interleukin-6 and soluble receptors without ischemia/reperfusion-induced effects. A strong correlation of the soluble receptors with interleukin-6 (p<0.01) could be detected in liver resection and gastrectomy. CONCLUSIONS: Uncomplicated liver resections were associated with a prolonged and increased release of soluble tumor necrosis factor receptors while no immunoreactivity could be detected. The strong correlation of soluble receptors with interleukin-6 may suggest an important role in the acute phase response of major operations.

Adult↗

PubMed1998

[Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis].

BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE. Pts were subdivided on the basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts with high AChRAb). Soluble adhesion molecules and cytokines were measured before the 1st and last PE, at the end of the 1st PE and in the samples of plasma filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the first PE and the course of PE led to the substantial decrease of serum levels of AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not, however, significantly influenced by both the single and the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS: Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in pts with MG indicated to the treatment by PE suggest some systemic activation of immune response which is more pronounced in pts with high circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion molecules due to their effective filtration, but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with synthetic membrane.

Adult↗

PubMed1996

Enzyme-linked immunosorbent assay detects a potential soluble form of the erythropoietin receptor in human plasma.

The erythropoietin receptor (EpoR) is a type I transmembrane protein that is a member of the family of hemopoietin receptors. Several members of this family have soluble receptor forms that are secreted by the cells rather than expressed on the cell surface. An alternatively spliced EpoR transcript has been described in human erythroid precursors that, if translated, would produce a truncated, soluble EpoR lacking the transmembrane domain. To determine if the human EpoR is expressed in a soluble form, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) for the EpoR, and we analyzed human serum and plasma. Sheep were immunized with a fusion protein (EREx) consisting of glutathione-S-transferase (GST) and the human EpoR extracellular domain. The sheep antiserum was affinity-purified on immobilized EREx, and then used in a two-stage antigen capture ELISA. The plasma from 20 normal subjects was studied with this assay. There was a wide variability in the levels of soluble EpoR in these subjects (range, <10-2,200 ng/ml). An average value of 550 +/- 735 ng/ml for soluble EpoR was obtained in these normals. Protein A adsorption of the test plasma prior to the assay had no effect on the values obtained. Assay of serum from the same normal subjects showed an average decrease of 88% in soluble EpoR levels compared to plasma. There was no correlation between hematocrit and soluble EpoR levels compared to plasma. There was no correlation between hematocrit and soluble EpoR level. This assay may have utility in the further elucidation of erythropoietin physiology.

Adult↗

PubMed2000

Soluble insulin-like growth factor II/mannose 6-phosphate receptor inhibits DNA synthesis in insulin-like growth factor II sensitive cells.

The soluble form of the insulin-like growth factor II (IGF-II)/mannose 6-P (IGF-II/M6P) receptor is released by cells in culture and circulates in the serum. It retains its ability to bind IGF-II and blocks IGF-II-stimulated DNA synthesis in isolated rat hepatocytes. Because these cells are not normally stimulated to divide by IGF-II in vivo, the effect of soluble IGF-II/M6P receptor on DNA synthesis has been further investigated in two cell lines sensitive to IGF-II; mouse 3T3(A31) fibroblasts, stimulated by low levels of IGF-II following priming by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) and Buffalo rat liver (BRL) cells, which secrete IGF-II and proliferate in the absence of exogenous growth factors. Soluble IGF-II/M6P receptor (0.2-2.0 microgram/ml) purified from a rat hepatoma cell line inhibited DNA synthesis (determined by dThd incorporation) in both cell lines. Basal DNA synthesis was very low in serum-free 3T3 cells, but high in serum-free BRL cells, possibly as a result of autocrine IGF-II production. The inhibitory effect was reversible in cells preincubated with soluble receptor prior to incubation with growth factors and could also be overcome by excess IGF-II. Soluble receptor was more potent in IGF-II-stimulated 3T3 cells and serum-free BRL cells than in BRL cells incubated with serum. Mean inhibition by four preparations of soluble receptor (1 microgram/ml) was 34.7% +/- 4.4% in BRL cells stimulated with fetal calf serum (FCS) (5%) compared to 54.8% +/- 4.2% in serum-free BRL cells (P = 0.05) and 60.6% +/- 6.5% (P = 0.02) in 3T3 cells stimulated by PDGF, EGF, and IGF-II. Soluble receptor had no effect on DNA synthesis in 3T3 cells stimulated with IGF-I. These results demonstrate that soluble receptor, at physiological concentrations, can block proliferation of cells by IGF-II and could therefore play a role in blocking tumor growth mediated by IGF-II.

Animals↗

PubMed2002

Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30.

CD30 is an unusual member of the TNF receptor superfamily with a duplicated segment within its extracellular domain that may function as an additional ligand binding site. The extracellular domain of CD30 is shed from cells and soluble CD30 levels are elevated in certain disease states. Soluble CD30 may bind to its ligand, CD153, with high affinity and block its interaction with membrane-bound CD30. We have generated soluble recombinant forms of CD30 and CD153 in order to characterize their interaction and assess their biological activity. Soluble trimeric CD153 bound to membrane-anchored CD30 with a relatively high affinity (K(D)=23 nM) and was effective in triggering cell death and TNF-alpha production in the presence of cross-linking antibodies. The affinity and kinetics of the interaction between soluble CD30 and CD153 were determined using the BIAcore biosensor. In contrast to other members of the TNF receptor superfamily, soluble monomeric CD30 bound to its ligand with high affinity (K(D)=4.5 nM) and prevented the interaction of cellular CD153 with immobilized CD30. Furthermore, soluble CD30 blocked cell death signals generated by cell surface-expressed CD30 effectively. These data suggest that soluble CD30 may have biological functions in vivo.

Animals↗

PubMedDate not supplied

Physical-chemical methods for determining bilirubin solubilities in simulated bile systems.

This report describes a rigorous physical-chemical approach to determine the solubilities of unconjugated bilirubin in model bile systems. In the absence of calcium ions, metastable and equilibrium solubilities can be obtained by acidimetric (HCl) titration of excess unconjugated bilirubin in aqueous solutions of simple and mixed conjugated bile salt micelles. The experiments must be performed with degassed water under argon, in dim light and at constant temperature and ionic strength. This approach provides metastable and equilibrium solubilities of unconjugated bilirubin at a unique pH, i.e., the precipitation pH (pHppt) of bilirubin in the bile salt system. Because high levels of supersaturation can be acidimetrically induced, equilibration is usually complete in less than 20 min. To obtain equilibrium solubilities of bilirubin in simulated bile systems at other pH values (less than pHppt greater than), it is necessary to perform equilibrium dissolution studies of crystalline diacid bilirubin in the presence of a strong buffer (at least 0.2 M). This method must, perforce, be the procedure of choice to estimate micellar bilirubin solubilities in the presence of calcium ions. Each dissolution experiment takes from 2 to 3 days, hence meticulous attention must be paid to the photochemical stability of bilirubin during the equilibration period, and appropriate precautions taken. Bilirubin solubilities obtained by both methods can be validated by titrating predetermined concentrations of unconjugated bilirubin spectrophotometrically in the model bile systems to the pH value at which saturation solubility was obtained. As a check of equilibration, it is imperative that bilirubin solubility values at the pHppt obtained by both dissolution and titrametric methods display satisfactory agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗

PubMed2006

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 2. Semipredictive or semiempirical models.

The solubility of stearic acid, ranitidine hydrochloride, and stavudine were predicted in selected organic solvents. The experimental solubility data of stearic acid and ranitidine hydrochloride were reported in previous work of the authors and stavudine's solubility was measured in this work. Equilibrium aqueous solubility of crystalline stauvudine was determined at controlled temperatures by stirring and filtration, with spectrophotometric quantification. The new model developed in Part 11 of this communication was modified as a semipredictive model with two adjustable parameters. Predicting the solubility data with the NRTL model using just one experimental point resulted in a big error while the modified new model and the UNIQUAC model showed much smaller errors. A new method was proposed in this work for predicting the solubility data of all polymorphs of a given compound using the experimental solubility data of one of the polymorphs of the same chemical compound. Although in general, the UNIQUAC model predictions were marginally superior, the new model is simpler and does not require the molecular parameters such as Van der Waals area and volume. The solubility prediction in a mixture of solvents using the NRTL and UNIQUAC models was also discussed.

2-Propanol↗

PubMed1976

Dissolution rates of high energy sulfathiazole--povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies.

Solubility studies were made to characterize the form of sulfathiazole controlling the rate of dissolution exhibited in previously reported dissolution rate studies of sulfathiazole coprecipitated with povidone. The aqueous solubility of the high energy form of sulfathiazole obtained using sulfathiazole--povidone coprecipitates was determined in the presence of polymer in solution. Its aqueous solubility in the absence of polymer was determined by extrapolation. The solubility value was much greater than either the supercooled melt or the crystalline forms of sulfathiazole. Stabilization of these sulfathiazole solutions supersaturated with respect to the more stable crystalline form was achieved by the addition of sufficient polymer to the solution to prevent nucleation of the crystalline form. The concentration of polymer required to prevent nucleation of the crystalline forms was much higher than the previously reported concentrations required to inhibit crystal growth of sulfathiazole. The ratio of the solubility value obtained for the coprecipitated sulfathiazole as compared with its crystalline form I was in agreement with the ratio of their dissolution rates obtained the plateau regions of the dissolution rate experiments reported previously. The extrapolated aqueous solubility values in the absence of povidone were obtained as a function of temperature and were utilized to obtain thermodynamic parameters. The difference in the heat of solution of the two forms of sulfathiazole from the slope of the van't Hoff plots of the extrapolated solubility values was 1618 cal/mole, in excellent agreement with the literature value. The free energy, enthalpy, and entropy at 27 degrees for the coprecipitated drug relative to its crystalline form I were 1125 cal/mole, 8439 cal/mole, and 24 eu, respectively, indicating the high degree of molecular randomness and lack of structure in these high energy systems. These results provide strong evidence for the presence of an amorphous state of sulfathiazole as the controlling phase of both the solubility and dissolution rate experiments involving the high energy form of sulfathiazole obtained by coprecipitation with povidone.

Crystallization↗

PubMed1984

Expanded solubility parameter approach. I: Naphthalene and benzoic acid in individual solvents.

An expanded solubility parameter system was tested in conjunction with the extended Hansen solubility approach and the UNIFAC method to calculate the solubilities of naphthalene and benzoic acid in polar and nonpolar solvents. The expanded parameter system is characterized by delta d for the dispersion force, delta p for dipolar forces, a basic or electron-donor parameter, delta b, and an acidic or electron-acceptor parameter delta a. The correlation between the calculated and observed solubilities of benzoic acid was increased by use of the four-parameter system. An indicator variable was required to bring the solubilities into line in strongly dipolar solvents such as N,N-dimethylformamide. For naphthalene, use of the four-parameter approach proved not to be an improvement over the three-parameter extended Hansen solubility approach. The UNIFAC method was not successful in calculating solubilities of benzoic acid in the 40 polar and nonpolar solvents. A triangular plot of the three Hansen parameters for benzoic acid, p-hydroxybenzoic acid, and methyl p-hydroxybenzoate illustrated the contributions of dispersion, dipolar, and Lewis acid-base (hydrogen bonding) interaction forces among the three benzoic acid compounds and the various classes of solvents. A multiple regression procedure for calculating the four partial solubility parameters of drug solutes was developed.

Benzoates↗

PubMed1984

Membrane solubility parameter and in situ release of theophylline.

The solubility of theophylline in polyethylene glycol 400-water binary mixtures was analyzed in terms of solute-solvent interaction using the solubility parameter principle of Hildebrand. Preliminary in situ (rat gut permeation) studies with the solvent mixtures having varying polarity as expressed by the solubility parameter showed that (a) the more alike the solubility parameter of theophylline (delta 2 = 14, as obtained from solubility studies) and the solubility parameter of the solvent mixture, the greater was the attraction of solvent for the drug (b) sufficient similarity must exist between the solubility parameter of theophylline and that of the intestinal mucosa to promote bioabsorption, and (c) from the above, it follows that there exists a competition between solvent and rat gut membrane for the drug. The solubility parameter of the solvent vehicle must be such that it does not impede absorption of the molecules into the intestinal mucosa.

Animals↗

PubMed1986

An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets.

B-Lymphocytes↗

PubMed1993

Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease.

The CD25 molecule, which corresponds to the p55 alpha chain of the interleukin-2 receptor, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-alpha therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722 +/- 27,001 vs. 331 +/- 145 units/ml in controls (mean +/- SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-alpha discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r = 0.84, P < 0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia.

Adult↗