Listening to the neurological teams for multiple sclerosis: the SMART project.

OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.

Informing MS patients on treatment options: a consensus on the process of consent taking.

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

PCR-based approach for qualitative molecular analysis of six neurotropic pathogens.

In the last few years, polymerase chain reaction analysis is frequently required to improve the detection of pathogen infections in central nervous system as a potential cause of neurological disorders and neuropsychiatric symptoms. The goal of this paper is to set up a fast, cheap and reliable molecular approach for qualitative detection of six neurotropic pathogens. A method based on PCR has been designed and implemented to guarantee the qualitative DNA detection of herpes simplex virus types 1 and 2 (HSVI/II), Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus (VZV), rubella virus (RUBV) and Toxoplasma gondii in the cerebrospinal fluid, where otherwise they are barely detectable. Each PCR assay was tested using dilutions of positive controls, which demonstrated a sensitivity allowing to detect up to 102 copies/ml in PCR and 10 copies/ml in real-time PCR for each pathogen. Once been set up, the protocol was applied to evaluate the cerebrospinal fluid from 100 patients with suspected infectious diseases of the central nervous system and 50 patients without any infection. The method allowed to identify 17 positive cerebrospinal fluid with polymerase chain reaction and 22 with real-time PCR (RT-PCR), respectively. Therefore, application of RT PCR allows a fast and sensitive evaluation of neurotropic DNA pathogens in the course of diagnostic routine within neurological units.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine.

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.

Overexpression of histamine H4 receptors in the kidney of diabetic rat.

OBJECTIVE AND DESIGN: The renal expression of H1 and H2 receptors has previously been demonstrated, while that of the H4 receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H4 receptor in the kidney of diabetic rats. MATERIAL OR SUBJECTS: 24 8-week-old male Wistar rats. TREATMENT: Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later. METHODS: Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H4 receptor, colocalization experiments were performed with a series of markers. RESULTS: H4 receptor is expressed in healthy rats, although at a very low level, and is strongly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H4 receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed. CONCLUSIONS: The results demonstrate, for the first time, that the H4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henlé and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease.

Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.

A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia.

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.

Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression.

BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) is highly expressed during inflammation and can promote the progression of colorectal cancer. Interactions between cancer cells and vascular endothelial cells are key events in this process. Recently, the selective COX-2 inhibitor, celecoxib, was shown to inhibit expression of the adhesion molecules, ICAM-1 and VCAM-1, in the human colon cancer cell line HT29 and to inhibit adhesion of HT29 cells to FCS-coated plastic wells. Here, we evaluated the effects of celecoxib on adhesion of HT29 cells to human umbilical vein endothelial cells (HUVEC), mediated by ICAM-1 and VCAM-1, to assess further the potential protective effects of celecoxib on cancer development. EXPERIMENTAL APPROACH: Celecoxib was incubated for 4 h with HT29 cells and HUVEC and adhesion was quantified by a computerized micro-imaging system. Expression analysis of ICAM-1 and VCAM-1 cell adhesion molecules was performed by western blot. KEY RESULTS: Celecoxib (1 nM-10 microM) inhibited, with the same potency, adhesion of HT29 cells to resting HUVEC or to HUVEC stimulated by tumour necrosis factor-alpha (TNF-alpha), mimicking inflammatory conditions. Analysis of ICAM-1 and VCAM-1 expression showed that celecoxib inhibited expression of both molecules in TNF-alpha-stimulated HUVEC, but not in resting HUVEC; inhibition was concentration-dependent and maximal (about 50%) at 10 microM celecoxib. CONCLUSIONS AND IMPLICATIONS: In conclusion, our data show that celecoxib inhibits HT29 cell adhesion to HUVEC and expression of ICAM-1 and VCAM-1, in stimulated endothelial cells. These effects may contribute to the chemopreventive activity of celecoxib in the development of colorectal cancer.

Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a colon cancer cell line (HT29).

BACKGROUND AND PURPOSE: We investigated the ability of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, to modulate expression of ICAM-1 and VCAM-1 in the colon cancer cell line HT29. EXPERIMENTAL APPROACH: We analysed the effect of celecoxib on ICAM-1 and VCAM-1 protein and mRNA expression in HT29 cells. Experiments were performed in the presence of mitogen-activated protein kinases (MAPK) inhibitors to evaluate the involvement of these kinases in this phenomenon. We evaluated adhesion of HT29 cells to FCS-coated plastic wells in the presence of celecoxib or MAPK inhibitors. Furthermore, we studied the effect of celecoxib on apoptosis. KEY RESULTS: Celecoxib down-regulated ICAM-1 and VCAM-1 expression in HT29 cells in a time- and dose-dependent way. Celecoxib reduced activation of p38 and p55 c-Jun terminal NH(2) kinase (JNK) MAPKs, but did not affect p46 JNK or p42/44 MAPK phosphorylation. Pretreatment with SB202190 or SP600125, specific inhibitors of p38 and JNK MAPKs, respectively, reduced ICAM-1 and VCAM-1 expression in HT29 cells dose-dependently. Adhesion of HT29 cells to FCS-coated plastic wells was inhibited dose-dependently by celecoxib, and also by SB202190 and SP600125. Celecoxib showed a pro-apoptotic effect, inducing Bax and BID but down-regulating Bcl-2. CONCLUSIONS AND IMPLICATIONS: Our findings show that celecoxib caused down-regulation of ICAM-1 and VCAM-1, affecting the adhesive properties of HT29 cells in a COX-2 independent way, inhibiting p38 and p55 MAPKs and activating a pro-apoptotic pathway.

A preliminary in vitro and in vivo study of the effects of new anthraquinones on neutrophils and bone remodeling.

Osteolysis, that is, progressive periprosthetic bone loss, is responsible for approximately 70% of aseptic loosening and implant failure. Usually, it is due to a granulomatous reaction wear-induced, leading to macrophage and osteoclast-mediated bone resorption. At present, there is no established prophylaxis or treatment for this process. For this purpose, as a preliminary investigation, we aimed to study the effects in two directions, inhibition of proinflammatory signals, and bone remodeling activity, of two newly synthesized anthraquinone molecules [N,N'-Diethylamino-2,6-anthraquinone-disulfonamide (GR375) and N,N'-(p-ethoxyphenyl)-2,6-anthraquinone-disulfon amide (GR377)]. Among the pro-inflammatory signals, the ability of the two anthraquinones to interfere with the production of superoxide anion (O(2) (-)), which was assumed as a marker of reactive oxygen species (ROS), was evaluated in an in vitro cell model by testing phagocytes, such as human neutrophils, challenged by the chemotactic agent N-formylmethionyl-leucyl-phenylalanine (FMLP). Both compounds inhibited O(2) (-) production, in a dose-dependent way, without exerting scavenger effects. An in vivo model was applied to investigate their effect on bone remodeling. Fifty-four female Wistar rats were divided into eight groups of six animals each, and a 4-week treatment was applied in two phases. A 25 mg/kg/os dose in the first phase and 12.5-6.25 mg/kg/os doses in the second one were employed. The tibia trabecular bone at the secondary spongiosa level was analyzed, and trabecular bone volume (%TBV), trabecular thickness (TbTh), and apatite lattice parameters were measured. At the highest doses of GR375 and GR377 the %TBV and the TbTh increased by 33.2, 34.6%, and 3.6 and 9.1%, respectively, whereas crystallographic parameters were not significantly different from the untreated group. Our results suggest a simultaneous antiinflammatory and antiosteoclastic activity of both drugs that encourages to perform further research. If it will be confirmed, they could be proposed in a variety of bone diseases, in particular, when acute inflammation is associated to osteolytic processes and, eventually, in the prevention and treatment of periprosthetic osteolysis.

Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils.

The neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonuclear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleukin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, [Ca(2+)]i, evoked by the chemokine. The priming effects of SP were abolished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4-11) and SP(6-11) but not the N-terminal peptide SP(1-7) shared the priming effects of SP. The selective NK-1 receptor agonist [Sar-9, MetO2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [betaAla-8]-NKA(4-10) or the selective NK-3 agonist senktide. Two selective NK-1 antagonists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demonstrated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated.

The inhibition of histamine uptake and metabolism by burimamide in the guinea-pig atrium and in mouse neoplastic mast cells, in vitro.

Burimamide, an H(2)-receptor blocking agent, has been shown capable of blocking the uptake and metabolism of [(14)C]-histamine, both in the guinea-pig isolated atrium and in murine neoplastic mast cells. This occurs even at concentrations far below the dose range capable of blocking the positive chronotropic effect of histamine in the isolated atrium. In the atrium, very low concentrations of burimamide were found capable of blocking histamine metabolism.

Enhanced responsiveness of ovalbumin-sensitized guinea-pig alveolar macrophages to tachykinins.

1. We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK2 receptor agonist [beta-Ala8]-NKA(4-10) to induce superoxide anion (O2-) production and prostanoid (prostaglandin E2, thromboxane B2) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea-pigs. 2. The dose-response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. 3. By evaluating the effects of [beta-Ala8]-NKA(4-10), we observed that not only was the concentration-response curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea-pigs. 4. This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). 5. Only small amounts of beta-glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. 6. These results indicate that AMs isolated from sensitized guinea-pigs show an increased responsiveness to NK2 receptor stimulation and further stress the role played by AMs in allergic lung diseases.

Interaction of histamine H1-and H2-receptor antagonists with histamine uptake and metabolism by guinea-pig isolated atrium and mouse neoplastic mast cells cells in vitro.

1. Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea-pig atrium and in mouse neoplastic mast cells. 2. Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide greater than chlorpheniramine greater than triprolidine greater than metiamide in the atrium; and burimamide greater than metiamide greater than triprolidine greater than chlorpheniramine, in the mase cells. 3. Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.

Characterization of ionotropic glutamate receptors in human lymphocytes.

The effect of L-glutamate (Glu) on human lymphocyte function was studied by measuring anti-CD(3) monoclonal antibody (mAb) or phytohaemagglutinin (PHA)-induced intracellular Ca(2+) ([Ca(2+)](i)) rise (Fura-2 method), and cell proliferation (MTT assay). Glu (0.001 - 100 microM) did not modify basal lymphocyte [Ca(2+)](i), but significantly potentiated the effects of anti-CD(3) mAb or PHA. Maximal [Ca(2+)](i) rises over resting cells were: 165+/-8 and 247+/-10 nM at 3.0x10(-2) mg ml(-1) anti-CD(3) mAb; 201+/-4 and 266+/-9 nM at 5.0x10(-2) mg ml(-1) PHA, in the absence or presence of 1 microM Glu, respectively. The Glu effect showed a bell-shape concentration-dependent relationship, with a maximum (+90+/-3% for anti-CD(3) mAb and +57+/-2% for PHA over Glu-untreated cells) at 1 microM. Non-NMDA receptor agonists (1 microM) showed a greater efficacy (+76+/-2% for (S)-AMPA; +78+/-4% for KA), if compared to NMDA (+46+/-2%), or Glu itself. Ionotropic Glu receptor antagonists completely inhibited the effects of the corresponding specific receptor agonists (1 microM). The IC(50) values calculated were: 0.9 microM for D-AP5; 0.6 microM for (+)-MK801; 0.3 microM for NBQX. Both NBQX and KYNA were able to abolish Glu effect. The IC(50s) calculated were: 3.4 microM for NBQX; 0.4 microM for KYNA. Glu (0.1 - 1 mM) did not change the resting cell proliferation, whereas Glu (1 mM) significant inhibited (-27+/-4%) PHA (1.0x10(-2) mg ml(-1))-induced lymphocyte proliferation at 72 h. In conclusion, human lymphocytes express ionotropic Glu receptors functionally operating as modulators of cell activation.

The antianaphylactic action of histamine H2-receptor agonists in the guinea-pig isolated heart.

The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. Nordimaprit and the selective H1-receptor agonist 2-pyridyl-ethyl-amine (2-PEA) did not modify the patterns of cardiac anaphylaxis. The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. The H2-receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2-receptors in cardiac anaphylaxis.

Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors.

1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10(-5) M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce O2-. production from guinea-pig AM, ED50 values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA greater than SP greater than NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK2 receptor agonist [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. production from guinea-pig AM; the NK1 receptor agonist [Pro9]-SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me,Phe7]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology.

Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.

1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf-acether (Paf) by studying their effects on Paf-induced relaxation and Paf-induced prostaglandin E2 (PGE2) production in histamine-contracted guinea-pig tracheal preparations. 2. Relaxation induced by Paf 4 microM in histamine-contracted guinea-pig tracheal preparations was 39.67 +/- 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine-contracted guinea-pig tracheal preparations. 3. WEB 2086 inhibited in a dose-related manner (IC50 = 21.2 nM) the relaxant effect induced by Paf and, at 1 microM, suppressed Paf-induced release of PGE2. 4. BN 52021 100 microM inhibited to about 60% Paf-induced relaxation of histamine-contracted guinea-pig tracheal preparations, but completely abolished Paf-induced increase in PGE2. 5. Both antagonists had no effects on relaxations induced by arachidonic acid 10 microM or PGE2 0.1-1 microM in histamine-contracted guinea-pig tracheal preparations. 6. The results are consistent with the presence of specific Paf receptors in guinea-pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf-induced relaxation in this experimental model.

Temperature dependence of [3H]PAF binding to washed human platelets.

Our results indicate that the binding of [3H]PAF to a single class of high affinity sites on human platelets is endothermic and largely entropy-driven. The increase in entropy can be attributed to the disorganization of water molecules bound to both receptor and ligand during the binding process.