Biomedical subjects

G Bartolini

Publications and source records attributed to G Bartolini.

At least 19 recordsLinked to original sources

PubMed2003

Trans-10,cis-12 CLA increases liver and decreases adipose tissue lipids in mice: possible roles of specific lipid metabolism genes.

Although consumption of CLA mixtures has been associated with several health effects, less is known about the actions of specific CLA isomers. There is evidence that the t10,c12-CLA isomer is associated with alterations in body and organ weights in animals fed CLA, but the mechanisms leading to these changes are unclear. The purpose of this study was to determine the effects of two commonly occurring isomers of CLA on body composition and the transcription of genes associated with lipid metabolism. Eight-week-old female mice (n = 11 or 12/group) were fed either a control diet or diets supplemented with 0.5% c9,t11-CLA or t10,c12-CLA isomers or 0.2% of the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist fenofibrate for 8 wk. Body and retroperitoneal adipose tissue weights were significantly lower (6-10 and 50%, respectively), and liver weights were significantly greater (100%) in the t10,c12-CLA and the fenofibrate groups compared with those in the control group; body and tissue weights in the c9,t11-CLA group did not differ from those in the control group. Livers from animals in the t10,c12-CLA group contained five times more lipids than in the control group, whereas the lipid content of the fenofibrate group did not differ from that in the control group. Although fenofibrate increased the mRNA for PPARalpha, t10,c12-CLA decreased it. These results suggest that PPARalpha did not mediate the effects of t10,c12-CLA on body composition. The CLA isomers and fenofibrate altered mRNA levels for several proteins involved in lipid metabolism, but the most striking difference was the reduction of mRNA for leptin and adiponectin in the t10,c12-CLA group. These initial results suggest that changes associated with energy homeostasis and insulin action may mediate the effects of t10,c12-CLA on lipid metabolism.

Acyl-CoA Oxidase↗

PubMed2002

Similar effects of c9,t11-CLA and t10,c12-CLA on immune cell functions in mice.

Published results regarding the effects of CLA on immune cell functions have ranged from stimulation to inhibition. In those studies, a mixture of CLA isomers were used, and food intake was not controlled. We have examined whether the discrepancies in the results of earlier studies may be due to the lack of controlled feeding and whether the two isomers of CLA may differ in their effects on immune cell functions. Three groups of C57BL/6 female mice were fed either a control, c9,t11-CLA-, or t10,c12-CLA (0.5 wt%)-supplemented diet, 5 g/d, for 56 d. At the end of the study, the number of immune cells in spleens, bone marrows, or in circulation; proliferation of splenocytes in response to T and B cell mitogens; and prostaglandin secretion in vitro did not differ among the three groups. Both CLA isomers significantly increased in vitro tumor necrosis factor alpha and interleukin (IL)-6 secretion and decreased IL-4 secretion by splenocytes compared to those in the control group. Thus, the two CLA isomers had similar effects on all response variables tested. The discrepancies among the results from previous studies did not seem to be caused by the differences in the isomer composition of CLA used.

Administration, Oral↗

PubMed2001

Colocalization prostacyclin (PGI2) synthase--caveolin-1 in endothelial cells and new roles for PGI2 in angiogenesis.

In vascular cells, prostacyclin (PGI2) synthase (PGI2s) has been localized in the endoplasmic reticulum of endothelial cells and in the nuclear and plasma membrane of smooth muscle cells. In human umbilical vein endothelial (HUVE) cells, we detected the enzyme in abundant cytoplasmic vesicles apparently originating from the plasma membrane and similar to those stained by gold-albumin, which interacts with a caveolar receptor. This prompted us to try a direct confocal microscopy approach aimed at colocalizing gold-albumin, caveolin-1, and PGI2 synthase. Moreover, the staining of HUVE cells with an anti-BiP7Grp78 antibody (a marker of endoplasmic reticulum) shows a perinuclear localization, sharply separated from PGI2 synthase localization. The results indicate that more than 80% of the enzyme resides in cellular sites costaining with caveolin-1 antibody and gold-albumin. This evidence was confirmed by the demonstration that PGI2 synthase and caveolin-1 coimmunoprecipitate in HUVE cell lysates and that they are associated to detergent-insoluble membrane domains in the same low-density fractions of a sucrose gradient. In addition, depletion of cellular cholesterol by mevalonate and methyl-beta-cyclodextrin leads to the shift of PGI2 synthase and caveolin-1 to higher density fractions of the gradient. Biochemical evidence about colocalization was supported by the use of a fusion protein glutathione S-transferase (GST)/caveolin-1, which retained either PGI2s purified from ram seminal vesicles or PGI2s present in HUVE cell lysates. Binding of PGI2s to caveolin "scaffolding domain" and to C-terminal region was deduced by using full-length GST--Cav-1, GST--Cav 61--101, and GST C- and N-terminal fusion proteins. A double approach based on the usage of filipin as a specific caveolae-disrupting agent and antisense oligonucleotides targeting PGI2 synthase mRNA suggests that the production of PGI2 in caveolae is likely to be connected to the regulation of angiogenesis, at least in vitro.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

The effect of conjugated linoleic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans.

Despite extensive research on conjugated linoleic acid (CLA) showing multiple beneficial effects in animal models, little is known about the role of dietary CLA in human health. To investigate if the beneficial effects of CLA seen in animal models are relevant to humans, we conducted a study with 17 healthy female volunteers who lived in the Metabolic Research Unit of the Western Human Nutrition Research Center for 93 d. This paper reports only the results from this study that are related to the effects of CLA supplementation on blood coagulation, platelet function, and platelet fatty acid composition. Throughout the study, the subjects were fed a low-fat diet (30 en% fat, 19 en% protein, and 51 en% carbohydrate) consisting of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n = 10) whose diet was supplemented with 3.9 g/d of CLA or a control group (n = 7) who received an equivalent amount of sunflower oil consisting of 72.6% linoleic acid with no detectable CLA. Platelet aggregation was measured in platelet-rich plasma using adenosine diphosphate, collagen, and arachidonic acid agonists. No statistical difference was detected between the amount of agonist required to produce 50% aggregation of platelet-rich plasma before and after the subjects consumed the CLA, with the exception of a decrease in response to collagen. This decrease was found in both control and intervention groups with no significant difference between the groups, suggesting that both linoleic acid (sunflower oil) and CLA might have similar effects on platelet function. The prothrombin time, activated partial thromboplastin time, and the antithrombin III levels in the subjects were determined. Again, there was no statistically significant difference in these three parameters when pre- and post-CLA consumption values were compared. The in vivo bleeding times were also unaffected by CLA supplementation (10.4 + 2.8 min pre- and 10.2 + 1.6 min postconsumption). Platelet fatty acid composition was not markedly influenced by the consumption of dietary CLA, although there was a small increase in the amount of the 9 cis,11 trans-18:2 isomer normally present in platelets after feeding CLA for 63 days. In addition, small amounts of the 8 trans,10 cis-18:2 and the 10 trans,12 cis-18:2 isomers were detected in the platelets along with traces of some of the other isomers. Thus, when compared to sunflower oil, the blood-clotting parameters and in vitro platelet aggregation showed that adding 3.9 g/d of dietary CLA to a typical Western diet for 63 d produces no observable physiological change in blood coagulation and platelet function in healthy adult females. Short-term consumption of CLA does not seem to exhibit antithrombotic properties in humans.

Adult↗

PubMed2001

The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans.

Conjugated linoleic acid (CLA) has been suggested by some animal studies to possess antiatherogenic properties. To determine, in humans, the effect of dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center. Throughout the study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en% protein, and 51 en% carbohydrate] that consisted of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n = 10) supplemented daily with capsules containing 3.9 g of CLA or a control group (n = 7) that received an equivalent amount of sunflower oil. The CLA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9 cis-,11 trans-18:2; 10.8% 8 trans-,10 cis-18:2; 15.3% 11 cis-,13 trans-18:2; and 14.7% 10 trans-,12 cis-18:2) and their corresponding cis/cis (6.74% total) and trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn on study days 30 (end of the stabilization period), 60 (midpoint of the intervention period), and 93 (end of the intervention period). Adipose tissue samples were taken on days 30 and 93. CLA supplementation for 63 d did not change the levels of plasma cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA in plasma increased from 0.28 +/- 0.06 to 1.09 +/- 0.31 (n = 10, P < 0.05) after the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts. CLA in adipose tissue was not influenced by the supplementation (0.79 +/- 0.18 to 0.83 +/- 0.19 wt%) (n = 10) and the 9 cis-,11 trans-variety was the only isomer present. Thus, contrary to findings from some animal studies, CLA does not seem to offer health benefits, in the short term, regarding the prevention of atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA was present in the plasma at any given time. No adverse effect of CLA supplementation was detected in this study.

Adipose Tissue↗

PubMed1997

The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans.

Arachidonic acid (AA) is the precursor of thromboxane and prostacyclin, two of the most active compounds related to platelet function. The effect of dietary AA on platelet function in humans is not understood although a previous study suggested dietary AA might have adverse physiological consequences on platelet function. Here normal healthy male volunteers (n = 10) were fed diets containing 1.7 g/d of AA for 50 d. The control diet contained 210 mg/d of AA. Platelet aggregation in the platelet-rich plasma was determined using ADP, collagen, and AA. No statistical differences could be detected between the aggregation before and after consuming the high-AA diet. The prothrombin time, partial thromboplastin time, and the antithrombin III levels in the subjects were determined also. There were no statistically significant differences in these three parameters when the values were compared before and after they consumed the high-AA diet. The in vivo bleeding times also did not show a significant difference before and after the subjects consumed the high-AA diet. Platelets exhibited only small changes in their AA content during the AA feeding period. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 1.5 g/d of dietary AA for 50 d to a typical Western diet containing about 200 mg of AA produces no observable physiological changes in blood coagulation and thrombotic tendencies in healthy, adult males compared to the unsupplemented diet. Thus, moderate intakes of foods high in AA have few effects on blood coagulation, platelet function, or platelet fatty acid composition.

Adult↗

PubMed1997

The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans.

Normal healthy male volunteers (n = 10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P < 0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.

Adipose Tissue↗

PubMed1997

Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans.

Data on the effect of dietary arachidonic acid (AA) (20:4n-6) on the synthesis of thromboxane and prostacyclin (PGI2) in humans are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20:4n-6 added isocalorically to a stabilization (low-AA) diet on the excretion of 11-dehydrothromboxane B2 (11-DTXB2) and 2,3-dinor-6-oxo-PGF1 alpha (PGI2-M). In a crossover design, 10 healthy men, living in a metabolic unit, were fed a diet (low-AA) containing 210 mg/d of 20:4n-6 for 65 d and an identical diet (high-AA) that contained 1.5 g/d of additional 20:4n-6 for 50 d. Three-day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry. Mean excretion of 11-dehydrothromboxane B2 was 515 +/- 76, 493 +/- 154, and 696 +/- 144 ng/d (SD; n = 10) during the acclimation (15 d) low-AA diet and high-AA diet periods, respectively (41% increase from low-AA to high-AA diet, P = 0.0037); mean excretion of PGI2-M was 125 +/- 40, 151 +/- 36, and 192 +/- 55 ng/d (SD; n = 10) during acclimation (15 d) low-AA and high-AA diets; P = 0.0143). Thus both the metabolites of thromboxane and PGI2 increase on the high-AA diet. Furthermore, both indicated changes in metabolite excretion may be associated with measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Post-transcriptional regulation of thromboxane A2 synthase in U937 cells.

Translation of mRNAs is a process usually tightly coupled to transcription of genes. However, there are examples of mRNA species which accumulate without being translated. Some mRNAs present in oocytes and ferritin mRNA are the most studied models. Studying the biogenesis of thromboxane A2 (TXA2) in the promonocytic line U937, we have noted that in proliferating cells high levels of TXA2 synthase mRNA are detectable by Northern blot, whereas no TXA2 could be recovered in the medium. This has been explained on the basis of Western blot experiments: TXA2 synthase was not detectable in proliferating cells, while a band of about 55 kd appears after treatment with the differentiating agent TPA. Immunofluorescence detection by confocal microscopy was in agreement with Immunoblot results. Thus, in U937 cells, TPA behaves as a regulator of translation of TXA2 synthase mRNA. We have further observed that the induced enzyme in U937 cells has many characteristics in common with the human monocytic enzyme: a long half life (> 24 hrs), a marked stability during catalysis and similar Km and Vmax values. Thus, U937 cells are a good model to study the mechanism by which a mRNA is efficiently translated only after differentiation has been triggered.

Animals↗

PubMed1995

Prostacyclin (PGI2) synthase is a constitutively expressed enzyme in human endothelial cells.

Biogenesis of prostanoids is under the control of some polypeptide growth factors. Cytosolic phospholipase A2, a form specific for arachidonic acid containing phospholipids, is activated by a translocation mechanism regulated by growth factors, while prostaglandin H synthase isoforms are induced de novo in several cell types. No information is available as far as PGI2 synthase is concerned. Human umbilical vein endothelial cells were cultured under conditions favoring proliferation or differentiation or capillary-like network formation in the presence of collagen gels. Basic fibroblast growth factor (bFGF 0.5-4 ng/ml) was used as a mitogen, interleukin-1 alpha (IL-1 alpha 10-60 UI/ml) as a differentiating agent, and prostacyclin (PGI2) biosynthesis was evaluated. Under the first condition, basal PGI2 production was unaffected while, in the presence of IL-1 alpha, a marked stimulation of PGI2 synthesis was observed. It is known that IL-1 alpha is a potent inducer of PGH synthase, while it is not known whether PGI2 synthase is also induced. Two lines of evidence indicate that PGI2 synthase is a constitutively expressed not inducible enzyme: (a) proliferating nonproducing cells when added with PGH2 produce an amount of PGI2 not different from the amount produced by cells stimulated with IL-1 alpha; (b) under this condition PGI2 synthase was immunodetectable either by immunofluorescence detected by confocal microscopy or by ELISA and, on microsomes isolated from endothelial cells, by Western blotting. It is concluded that the limiting step in the conversion arachidonate-PGI2 is represented solely by the level of PGH synthase. These results strongly suggest, but do not prove, the constitutive nature of the enzyme. The final demonstration requires the availability of a probe to detect mRNA level, a trial we are carrying out at the moment.

Cell Division↗

PubMed1995

Possible involvement of prostaglandin H synthase-1 induction in the differentiation of U-937 cells.

The promyelocytic human cell line U937, cultured in the presence of TPA and/or vit. D3, differentiates to monocytes and to macrophage-like cells. A potent stimulus for differentiation is represented also by colony stimulating factor-1 (CSF-1). Since this factor is a strong inducer of PGH synthase in human monocytes, we have investigated whether this event may be connected to the differentiation of U937. We have found that TPA, in the presence of serum, increased the production of thromboxane B2 (TXB2) 4-5 fold, while DMSO, which induced differentiation to neutrophils, was not active. Here we report studies indicating that the effect of protein and RNA synthesis inhibitors on prostanoid production, in cells incubated in the presence of CSF-1 (or FCS), can be correlated with an inductive event carried out by the growth factor, as demonstrated by the use of Western and Northern blotting procedures. However, while in human monocytes PGH-s and its mRNA are absent in controls and are expressed at high levels in CSF-1 stimulated cells, in U937 cells exposed to TPA, PGH-s mRNA was clearly detected by Northern blots, but its translation product was expressed at low level, and cells generated low amounts of TXA2 (13% of maximal production). After incubation with CSF-1 (or FCS) mRNA levels were only slightly modified, but large amounts of TXA2 accumulated in the medium. We have interpreted these findings by suggesting that CSF-1 is capable not only of regulating the expression of the gene encoding PGHs, but also of acing translationally to regulate the expression of its mature mRNA.

Blotting, Western↗

PubMed1994

Thromboxane A2 synthase activity in platelet free human monocytes.

Soon after platelets, the highest amounts of thromboxane A2 (TXA2) can be detected in human monocytes activated by serum. Using platelet-free human monocytes, we have shown that foetal calf serum (FCS) induces prostaglandin H synthase (PGH synthase) after 16 h of incubation, as shown by the use of transcriptional inhibitors and Western blotting. The effect of serum can be in part mimicked by recombinant colony stimulating factor-1 (hr CSF-1). It is not known whether the limiting step leading from arachidonate to TXA2 is represented solely by the level of PGH synthase or also by the level of TXA2 synthase. We approached this problem by using a Western blot specific for the enzyme, as well as by using PGH2 as substrate. The results show that TXA2 synthase is constitutively expressed in monocytes, i.e., its levels were high soon after their isolation, and similar to those observed after 24 h of incubation with serum. However TXA2 failed to be synthesized until at least 3 h of incubation, and the pattern of synthesis was dependent on the kinetics of PGH synthase induction. In any condition in which TXA2 synthase was immunodetectable, using PGH2 as substrate a high rate of conversion to TXB2 could be detected. Experiments with actinomycin D and cycloheximide indicate that the half-life of TXA2 synthase was longer than 16 h, therefore much longer than that of PGH synthase, that the gene coding for it is fully active in resting monocytes, and that the conversion of arachidonate to TXA2 induced by serum or CSF-1 is dependent solely on the de novo synthesis of PGH synthase.

Apoenzymes↗

PubMed1990

Prostanoids as second messengers of polypeptide growth factors.

Prostaglandin H synthase (PGHs), also known as cyclooxygenase, is an unstable enzyme whose mRNA has an half life of 10 minutes. Some polypeptide factors have been reported to induce the enzyme in target cells. We have purified and characterized a component of animal sera which behaves as a potent inducer of human monocyte PGHs. This factor, called serum monocytotropic factor, has been identified in human platelets and it appears to be structurally and biochemically different from identified platelet factors, such as platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-beta), while showing strong similarities to colony stimulating factor 1 (CSF-1), so far undetected in platelets. Moreover, we have shown, by immunoblot analysis, that CSF-1 behaves as a potent and specific inducer of monocyte PGHs. The hypothesis that prostanoids may be considered as second messengers of platelet CSF-1 like factor, as well as of other growth factors and that PGHs induction plays a pivotal role in this process, will be illustrated.

Animals↗

PubMed1990

Interleukins and interferons: yin-yang modulators of PGH synthase in human macrophages.

Prostaglandin H synthase (PGHs) not only is an unstable enzyme, mainly when it is challenged with substrate, but its mRNA is one of the shortest lived species so far identified in mammalian cells. Therefore, signals regulating its level are critical for the role it plays in many cells. The expression of genes coding for PGHs appears to be under the control of polypeptide growth factors. This is in accordance with our previous data showing that a colony stimulating factor-1 (CSF-1)-like factor induces the de novo synthesis of PGHs in human monocytes, as demonstrated by immunoblotting. Here we extend this concept by showing that interleukin (IL)-1 alpha behaves as a potent inducer of PGHs in human macrophages, as indicated by the block in its action due to the addition of RNA and protein synthesis inhibitors. Interferons (IFNs) alpha and beta, however, inhibit prostanoid production in a dose-dependent fashion mainly when macrophages activated by serum are tested. Thus, the PGHs system appears to be under a fine control, CSF-1 being the main regulator during the differentiation from pro-monocyte to monocyte and from monocyte to macrophage, and IL-1 (and perhaps IL-2) as well as IFN alpha and beta, the regulators during differentiation and/or proliferation of human macrophages.

Cycloheximide↗

PubMed1989

Prostaglandin and thromboxane biosynthesis in isolated platelet-free human monocytes. III. The induction of cycloxygenase by colony stimulating factor-1.

Previous observations showing the presence in the serum of a component capable of regulating prostanoid biosynthesis in human cultured monocytes, have led us to suspect its presence in human platelets. We have purified this serum monocytotropic factor (SMF) and have shown its identity with a component of platelet membranes. Surprisingly its structure appeared to be very similar to that of a polypeptide growth factor never before identified in platelets: the colony stimulating factor-1 (CSF-1 or M-CSF). Here we show that SMF and CSF-1 have very similar biological properties. Thus, CSF-1 when released from human platelets is capable of triggering the differentiation pathway leading from blood monocytes to resident macrophages. It is likely that cycloxygenase induction plays a pivotal role in these events.

Chromatography, High Pressure Liquid↗

PubMed1989

Immune dysfunction in primary biliary cirrhosis. II. Increased production of prostaglandin E.

In a previous study we observed that after in vitro treatment with indomethacin, lymphocyte response to phytohaemagglutinin (PHA) in primary biliary cirrhosis (PBC) patients was higher than that of controls. We know that indomethacin also inhibits prostanoid production, and thus in the present work we directly measured prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production by mononuclear cells and monocytes from 12 PBC patients, 11 control subjects, and three control disease patients (alcoholic cirrhosis, AC). PHA-stimulated enriched monocytes from PBC patients produced approximately threefold more PGE2 (after 48 h of culture) than did normal and AC monocytes (P less than 0.05). TXB2 production was similar in all groups studied. We also made cultures in which PBC-purified lymphocytes proliferated better than PBC mononuclear cells (i.e. lymphocytes plus monocytes). Thus, a monocyte population producing PGE2 could be responsible, at least in part, for the hyporesponsiveness to PHA observed in PBC patients.

Humans↗

PubMed1989

A conjugate of prednisolone with albumin is pharmacologically active in macrophages.

In order to selectively deliver prednisolone to macrophages, this drug was coupled to human albumin. In experiments in vitro the conjugate entered into macrophages in much higher amounts than in fibroblasts; in the former cells it was pharmacologically active as demonstrated by the inhibition of prostaglandin E2 and thromboxane A2 production. Prednisolone-albumin conjugate might be useful in research on steroids; moreover in some pathological conditions it might produce the therapeutic effects of these drugs without causing their side effects.

Albumins↗

PubMed1988

Purification and partial characterization of serum monocytotropic factor, a platelet-derived cyclooxygenase-inducing polypeptide.

It has previously been shown that a heat- and acid-stable component of human and animal sera was capable of stimulating prostanoid biosynthesis in human blood monocytes, very probably by a mechanism involving cyclooxygenase induction. Many physico-chemical characteristics of this factor are similar to those of identified platelet factors. Here we show that human platelets are a rich source of this factor (serum monocytotropic factor) and that results from experiments using arachidonic acid or thrombin as releasers are consistent with its presence in platelet membranes. Serum monocytotropic factor has been purified 1500-fold by three chromatographic steps. Purification was more difficult when starting from platelet releasates or lysates. The purified serum monocytotropic factor had an apparent molecular mass of 70,000 as judged by Sephadex G-75 chromatography and by polyacrylamide gel electrophoresis; however, when subjected to HPLC on a gel permeation column in the presence of 6 M urea, one major peak corresponding to a relative molecular mass (Mr) of 30,000-35,000 was observed, which suggests a homodimeric structure. It is therefore very likely that human platelets store, in addition to the two well-identified polypeptide growth factors, platelet-derived growth factor and transforming growth factor-beta, a third polypeptide capable of regulating prostanoid production in monocytes.

Arachidonic Acid↗