Molecular basis for the activation of PAF receptor by PAF.

Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-Å structure of the PAF-bound PAFR-Gi complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation-π interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane-side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis.

HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation.

The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid-liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13-/- mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.

Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels.

Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca2+ influx pathways responsible. PAF (10-9-10-6 M) contracted EMM in a concentration-dependent manner. PAF (10-6 M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10-5 M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10-6 M)-induced contractions were abolished by extracellular Ca2+ removal but were not affected by diltiazem [a voltage-dependent Ca2+ channel (VDCC) inhibitor, 10-5 M]. PAF (10-6 M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca2+ channel (ROCC) inhibitor, 3 × 10-5 M], SKF-96365 [an ROCC and store-operated Ca2+ channel (SOCC) inhibitor, 3 × 10-5 M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca2+ influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.

Effect of platelet-activating factor on food intake, cloacal temperature, voluntary activity and crop emptying rate in chicks.

Platelet-activating factor (PAF) plays a significant role in several leucocyte functions, including platelet aggregation and inflammation. Additionally, PAF has a role in the behavioral and physiological changes in mammals. However, the effect of PAF has not been well studied in birds. Therefore, the study aimed to determine if PAF affects feeding behavior, voluntary activity, cloacal temperature, and feed passage through the digestive tract in chicks (Gallus gallus). We also studied the involvement of PAF in the innate immune system induced by lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria. Both intraperitoneal (IP) and intracerebroventricular (ICV) injections of PAF significantly decreased food intake. IP injection of PAF significantly decreased voluntary activity and slowed the feed passage from the crop, whereas ICV injection had no effect. Conversely, ICV injection of PAF significantly increased the cloacal temperature, but IP injection had no effect. The IP injection of LPS significantly reduced the mRNA expression of lysophosphatidylcholine acyltransferase 2, an enzyme responsible for PAF production in the heart and pancreas. On the other hand, LPS significantly increased the mRNA expression of the PAF receptor in the peripheral organs. The present study shows that PAF influences behavioral and physiological responses and is related to the response against bacterial infections in chicks.

Lysophospholipid Acyltransferase 9 Promotes Emphysema Formation via Platelet-activating Factor.

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. PAF (platelet-activating factor), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases such as bronchial asthma and COPD. We focused on LPLAT9 (lysophospholipid acyltransferase 9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophages (AMs). LPLAT9 was predominant and upregulated in AMs, particularly monocyte-derived AMs, in patients with COPD. To identify the function of LPLAT9/PAF in AMs in the pathogenesis of COPD, we exposed systemic LPLAT9-knockout (LPALT9-/-) mice to cigarette smoke (CS). CS increased the number of AMs, especially the monocyte-derived fraction, which secreted MMP12 (matrix metalloprotease 12). Also, CS augmented LPLAT9 phosphorylation/activation on macrophages and, subsequently, PAF synthesis in the lung. The LPLAT9-/- mouse lung showed reduced PAF production after CS exposure. Intratracheal PAF administration accumulated AMs by increasing MCP1 (monocyte chemoattractant protein-1). After CS exposure, AM accumulation and subsequent pulmonary emphysema, a primary pathologic change of COPD, were reduced in LPALT9-/- mice compared with LPLAT9+/+ mice. Notably, these phenotypes were again worsened by LPLAT9+/+ bone marrow transplantation in LPALT9-/- mice. Thus, CS-induced LPLAT9 activation in monocyte-derived AMs aggravated pulmonary emphysema via PAF-induced further accumulation of AMs. These results suggest that PAF synthesized by LPLAT9 has an important role in the pathogenesis of COPD.

How to handle off-label prescriptions of rupatadine, a second-generation antihistamine and PAF antagonist: a review.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.

Evidence for the involvement of keratinocyte-derived microvesicle particles in the photosensitivity associated with xeroderma pigmentosum type A deficiency.

Photosensitivity can be due to numerous causes. The photosensitivity associated with deficiency of xeroderma pigmentosum type A (XPA) has been previously shown to be associated with excess levels of the lipid mediator platelet-activating factor (PAF) generated by the keratinocyte. As PAF has been reported to trigger the production of subcellular microvesicle particles (MVP) due to the enzyme acid sphingomyelinase (aSMase), the goal of these studies was to discern if PAF and aSMase could serve as therapeutic targets for the XPA deficiency photosensitivity. HaCaT keratinocytes lacking XPA generated greater levels of MVP in comparison to control cells. Mice deficient in XPA also generated enhanced MVP levels in skin and in plasma in response to UV radiation. Use of a genetic strategy with mice deficient in both XPA and PAF receptors revealed that these mice generated less MVP release as well as decreased skin erythema and cytokine release compared to XPA knockout mice alone. Finally, the aSMase inhibitor imipramine blocked UV-induced MVP release in HaCaT keratinocytes, as well as XPA knockout mice. These studies support the concept that the photosensitivity associated with XPA involves PAF- and aSMase-mediated MVP release and provides a potential pharmacologic target in treating this form of photosensitivity.

The correlation between serum IL-9, PAF and total IgE, IFN -γ, IL-4 levels in patients with chronic spontaneous urticaria / 中国医师杂志

Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.

Correlation of serum interleukin-9 and platelet-activating factor levels with total IgE levels, disease severity and disease course in patients with chronic spontaneous urticaria / 中华皮肤科杂志

Objective:To explore the relationship of serum interleukin (IL) -9 and platelet-activating factor (PAF) levels with serum total immunoglobulin E (IgE) levels, disease severity and disease course in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 60 patients with active CSU were collected from Department of Dermatology, the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 (active CSU group), and divided into mild group, moderate group and severe group according to 7-day urticaria activity score (UAS7). After 28-day standard antihistamine therapy, the patients whose condition became stable were included in the stable CSU group. During the same period, 30 health examinees were included in the healthy control group. Peripheral venous blood samples were collected from the subjects in each group, enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of IL-9 and PAF, and immunoturbidimetric assay to detect the serum total IgE level. Correlations of serum IL-9 and PAF levels with serum total IgE levels, UAS7 scores and disease courses were analyzed in patients with CSU. One-way analysis of variance was used for comparisons among multiple groups, least significant difference- t test for multiple comparisons, and Pearson correlation analysis for correlation analysis. Results:Totally, 28 males and 32 females were included in the active CSU group, their age ranged from 11 to 68 years (34.68 ± 8.62 years), and the disease duration ranged from 2 months to 7 years (1.42 ± 0.41 years). In the healthy control group, 14 were males and 16 were females, and their age ranged from 10 to 70 years (35.06 ± 7.89 years). According to UAS7, 12, 26, and 22 patients were diagnosed with mild, moderate and severe CSU respectively, and 22 were included in the stable CSU group after standard treatment. The levels of serum IL-9, PAF and total IgE significantly differed among the active CSU group, stable CSU group and healthy control group (IL-9: 144.34 ± 23.19 vs. 109.25 ± 20.77 vs. 107.23 ± 19.23 pg/ml; PAF: 362.45 ± 51.45 vs. 223.18 ± 32.46 vs. 221.23 ± 28.38 pg/ml; total IgE: 168.12 ± 32.48 vs. 24.04 ± 7.04 vs. 21.76 ± 5.95 IU/ml; F = 38.80, 148.38, 499.12, respectively, all P < 0.001), and were significantly higher in the active CSU group than in the stable CSU group and healthy control group (all P < 0.05), while there was no significant difference between the stable CSU group and healthy control group (all P > 0.05). Pearson correlation analysis showed that the serum IL-9 and PAF levels were positively correlated with serum total IgE levels and UAS7 scores (all P < 0.05), but not correlated with the disease course (both P > 0.05) . Conclusion:Serum IL-9 and PAF levels in patients with active CSU were markedly elevated along with the increase in disease severity, and closely correlated with serum total IgE levels.

Trombocitopenia inducida por heparina y síndrome de trombo blanco en paciente con SARS-CoV-2 / SARS-CoV-2 patient with heparin-induced thrombocytopenia and white thrombi syndrome / Trombocitopenia induzida por heparina e síndrome de trombo branco em paciente com SARS-CoV-2

Resumen: La trombocitopenia inducida por heparina es una entidad clínica infrecuente; sin embargo, la amplia y masiva utilización de anticoagulantes en épocas de pandemia por COVID-19 pone de manifiesto una realidad evidente a la cual no podemos escapar. Presentamos el caso de un paciente masculino en la sexta década de vida con SARS-CoV-2, quien luego de la administración de heparina en el escenario de una enfermedad pulmonar tromboembólica desarrolló consumo plaquetario asociado a presencia de anticuerpos antifactor de agregación plaquetaria 4.

Abstract: Heparin-induced thrombocytopenia is an uncommon clinical entity, however the wide and massive use of anticoagulants in times of pandemic by COVID-19 reveals an evident reality and we can not escape. we present the case of a male patient in sixth decade of life with SARS-CoV-2 who after the administration of heparin in the clinical setting of thromboembolic lung disease development platelet consumption associated with the presence of antibodies anti platelet activating factor 4.

Resumo: A trombocitopenia induzida por heparina é uma entidade clínica rara, no entanto, a ampla e massiva utilização de anticoagulantes em tempos de pandemia de COVID-19 revela uma realidade óbvia à qual não podemos fugir. Apresentamos o caso de um doente do sexo masculino na sexta década de vida com SARS-CoV-2 que, após administração de heparina no contexto de doença pulmonar tromboembólica, desenvolveu consumo de plaquetas associado à presença de anticorpos anti-fator de agregação plaquetária 4.

Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.@*METHODS@#147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.@*RESULTS@#At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.@*CONCLUSION@#The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.

Chemical Constituents and Biological Activities of Mitrella Kentii (Blume) Miq. Leaf Oil (Komponen Kimia dan Aktiviti Biologi Minyak Daun Mitrella Kentii (Blume) Miq.) / Jurnal Sains Kesihatan Malaysia

@#Chemical constituents and biological activities of the Mitrella kentii leaf oil were investigated in this study. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to determine the chemical constituents of the oil. The oil was evaluated for its ability to inhibit prostaglandin E2 (PGE2 ) and thromboxane B2 (TXB2 ) productions in human whole blood using a radioimmunoassay technique. Its inhibitory effect on plateletactivating factor (PAF) receptor binding with rabbit platelets using 3 H-PAF as a ligand and its free radical scavenging effect on DPPH were also investigated. Caryophyllene oxide (33.8%w/w), E,Z-farnesol (6.9%), benzyl benzoate (6.5%w/w) and viridiflorol (6.5%w/w) were among the major components of the oil. Even though weak inhibitory activities were observed in both PGE2 and TXB2 assays, significant results were obtained in both PAF receptor binding inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effect with IC50 value of 6.6 µg/mL and 155.6 µg/mL respectively. These promising activities warrant the development of the oil as an anti-inflammatory agent.

Compound Kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway / 中国药理学与毒理学杂志

OBJECTIVE Compound Kushen injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Japonicae). Clinically, it is used as the adjuvant treat?ment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. METHODS T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice. For evaluating micro?vascular permeability, Evans blue extravasation assay was used. Platelet-activating factor (PAF), serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) were measured by ELISA. RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alka?loids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stron?ger and could be abolished by blocking de novo pathway. CONCLUSION In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our find?ings may provide a potential approach for preventing and treating CKI-induced IHRs.

Effect of Wenjingtang on Levels of Serum Platelet Activating Factor and β-endorphins in Primary Dysmenorrhea Patients with Cold Stagnation and Blood Stasis Syndrome / 中国实验方剂学杂志

Objective::To explore the effect of Wenjingtang on the levels of serum platelet activating factor (PAF) and β-endorphins in primary dysmenorrhea patients with cold stagnation and blood stasis syndrome. Method::The 120 cases of dysmenorrhea treated at Second Affiliated Hospital, Heilongjiang University of Chinese Medicine from March 2016 to December 2017 were selected as the observation subjects, and divided into control group and observation group according to the random number table method, with 60 cases in each group. The control group was treated with ibuprofen capsules, while the observation group was treated with Wenjingtang and ibuprofen capsules. Dysmenorrhea symptom scores, clinical efficacy, recurrence condition and serum levels of platelet activating factor and β-endorphins were compared before and after treatment. Result::After treatment, the dysmenorrhea symptom scores decreased significantly in both groups, and the scores of patients in observation group were lower than those in control group (P<0.05). After treatment, the total efficiency in observation group was 95%, which was significantly higher than 83.33% in control group (P<0.05). The level of serum PAF decreased significantly in two groups, and the serum PAF in observation group was significantly decreased compared with control group (P<0.05). The level of serum beta-endorphins in observation group was significantly higher than that of control group (P<0.05). After half a year, the recurrence rate of the observation group was 5%, which was significantly lower than 30% of control group (χ2=12.987, P<0.01). Conclusion::Wenjingtang contributes to the reduction of dysmenorrhea symptoms scores in primary dysmenorrhea patients with cold stagnation and blood stasis syndrome, and can improve the clinical efficacy, reduce the serum PAF level and increase the concentration of β-endorphins, reduce the recurrence rate, improve the quality of life of patients, and it is worth promoting.

Mesenchymal Stromal Cells Modulate PAF-stimulated Equine Alveolar Macrophages

Abstract Platelet-activating factor (PAF) is a potent proinflammatory mediator that is produced in increased amounts in the lungs of asthmatic humans and horses. The present pilot study, shows that mesenchymal stromal cells can modulate alveolar macrophage function in asthma, interfering in the activity of PAF, being another potential pathway for mesenchymal stromal cells benefits in asthma.

Effect of Buyanghuanwu decoction on the expression of platelet activating factor after acute spinal cord injury in rats / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of Buyanghuanwu decoction on platelet activating factor expression in spinal cord tissue of model of acute upper cervical spinal cord injury in rats.</p><p><b>METHODS</b>Sixty SPF grade 3-month-old female Wistar rats were randomly divided into sham operation group, model group, methylprednisolone group and Buyanghuanwu decoction (Traditional Chinese Medicine group, TCM), with 15 rats in each group. The first day after the modeling, the methylprednisolone group were treated by injection of the tail vein for a total of 24 h, the first dose of 30 mg/kg, followed by a dose of 5.4 mg/kg·h, and 1 time per 4 h. The traditional Chinese medicine group was prepared with a medium dose of Buyanghuanwu decoction granules which were prepared into a solution containing 2 g/ml of granules, 3.5 g/kg per day gavage, was equivalent to 1 time the amount of adult consumption. The model group and the sham operation group were given equal volume of normal saline for 2 times a day for 2 weeks. The recovery of nerve function was evaluated by BBB classification at 1, 3, 7, 14 days after treatment. The expression of PAF in the segment of spinal cord injury was detected by double antibody sandwich (ELISA) method at 1, 7, and 14 d postoperatively.</p><p><b>RESULTS</b>At the first day after treatment, BBB score in model, TCM and methylprednisolone groups were lower than that of sham operation group(<0.01), but there was no difference among the three groups(>0.05). At 7, 14 days afer treatment, BBB score in TCM and methylprednisolone groups were higher than that of model group significantly(<0.01); but there were no significant difference between TCM group and methylprednisolone group(>0.05). PAF expression in TCM group and methylprednisolone group were lower than that of model group at 7, 14 day afer treatment significantly (<0.05); but there were no significant difference between TCM group and methylprednisolone group (>0.05).</p><p><b>CONCLUSIONS</b>Buyanghuanwu decoction treatment after acute upper cervical spinal cord injury can significantly improve locomotor recovery by inhibiting the expression of PAF.</p>

Effects of decompression combined with electro-acupuncture on rat with acute severe upper cervical spinal cord compression injury / 中国骨伤

<p><b>OBJECTIVE</b>To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury.</p><p><b>METHODS</b>Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method.</p><p><b>RESULTS</b>BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher(<0.05); and there was no significant difference between group C and group D(>0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E (>0.05), group C was lower than the other groups (<0.05); the concentration of tissue PAF, there was no significant difference between group A and group B(>0.05), group D was significantly higher than that of group A, B, and C(<0.05), group E was the highest one than that of the other groups(<0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar (>0.05), group C was higher than that of group A and B(<0.05), group D was higher than group A, B and C(<0.05), group E was the highest than that of group A, B, C and D (<0.05).</p><p><b>CONCLUSIONS</b>Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue.</p>

Effect of compatibility of ginkgolide A, ginkgolide B and ginkgolide K / 中国中药杂志

To investigate the best active compatibility of ginkgolide A, B and K (GA，GB，GK). The effects of GA, GB, GK alone, combinations of each two of them, and combinations of these three components on platelet-activating factor (PAF)-induced platelet aggregation activity and rat cerebral ischemia reperfusion model (tMCAO) were compared in this study. Different compatibilities of GA, GB and GK could significantly reduce the maximum aggregation rate of PAF-induced platelet aggregation, and the effect was most obvious in combination of the three. Different compatibilities of GA, GB and GK could alleviate the neural function, cerebral infarction volume and cerebral edema in the tMCAO model of rats to different degrees, and the effect of combinations of the three was stronger than those of combinations of two and single use. The combination of all of GA, GB and GK had the strongest effect on nerve injury caused by anti-platelet aggregation in tMCAO rats.

Research progress of platelet activating factor(PAF) receptor antagonist / 中国中药杂志

Platelet activating factor(PAF), an endogenous synthesized phospholipid transmitter, has widely biological activities. It has "signal transmission" effect in various life processes, but abnormality of concentration will promote or aggravate the diseases, such as, cerebral ischemia, myocardial injury, multi-organ failure, asthma, injury of liver and kidney, severely affecting the normal life activities of body. In recent years, with the development of medical science and technology, more and more attention has been paid to the research of platelet activating factor receptor antagonist. Components of animals, plants, microbial fermentation, and synthetic composition all can reflect such activity. Ginkgolide B and cytopone are the most representative herbal compositions at present. This paper referred to the research status of platelet activating factor receptor antagonist in recent years, made a summary of the researches on biological effect of platelet activating factor and platelet receptor antagonist of different sources, so as to provide a reference for the exploration of effective and safe platelet activating factor receptor antagonists.

Effect of combined domestic clopidogrel and tongxinluo on major adverse cardiovacular events after PCI / 中华老年心脑血管病杂志

Objective To study the platelet inhibition rate of foreign clopidogrel,domestic clopidogrel,combined domestic clopidogrel and tongxinluo and their effct on major adverse cardiovacular events (MACE) after PCI.Methods Two hundred and twenty patients after PCI were divided into foreign clopidogrel treatment group (n=77),domestic clopidogrel treatment group (n=80),combined domesticclopidogrel and tongxinluo treatment group (n =63).The high platelet reactivity (HPR) in 3 groups was detected by thrombelastography after PCI.The incidence of MACE in 3 groups was compared.Results The incidence of left anterior descending branch lesion was lower,the number of sacculi was smaller,and the incidence of HPR was higher in foreign clopidogrel treatment group than in domestic clopidogrel treatment group and combined domestic clopidogrel and tongxinluo treatment group after PCI (63.6％ vs 87.5％ vs 77.8％,P=0.002;2.3±1.1 vs 2.8±1.4 vs 2.7±1.5,P=0.026;24.7％ vs 21.3％ vs 11.1％,P=0.030).The incidence of HPR was significantly higher in foreign clopidogrel treatment group than in combined domestic clopidogrel and tongxinluo treatment group (24.7 ％ vs 11.1％,P =0.040).No significant difference was found in the incidence of MACE in 3 groups (P ＞ 0.05).Conclusion The incidences of MACE of domestic clopidogrel and foreign clopidogrel are similar.Combined clopidogrel and tongxinluo can improve the platelet inhibition rate after PCI.