Aldo-keto reductase family member C3(AKR1C3)promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α

Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.

Prostaglandin F_(2α)synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F_(2α)-dependent and F_(2α)-independent mechanism

BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.

The antioxidant trolox inhibits aging and enhances prostaglandin E-2 secretion in mesenchymal stem cells

Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation,differentiation,and immune regulation.However,during in vitro expansion,MSCs are prone to aging,which largely limits their application.Prostaglandin E-2(PGE-2)is a key effector secreted by MSCs to exert immunomodulatory effects.By screening the compound library for PGE-2 secretion,the antioxidant trolox was verified as a stimulator of MSCs to secrete PGE-2.The effect of antioxidant trolox on biological characteristics of MSCS,including aging,proliferation,and gene expression,was examined.The results demonstrated that trolox can resist aging,promote proliferation,and enhance PGE-2 secretion of MSCs without affecting their surface marker expression.Furthermore,trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects.Thus,trolox addition might be beneficial for MSCs expansion and their application.

Intra-arterial lipo-prostaglandin E1 infusion for arterial spasm in liver transplantation:A case report

BACKGROUND Hepatic artery obstruction is a critical consideration in graft outcomes after living donor liver transplantation.We report a case of diffuse arterial vasospasm that developed immediately after anastomosis and was managed with an intra-arterial infusion of lipo-prostaglandin E1(PGE1).CASE SUMMARY A 57-year-old male with hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma underwent ABO-incompatible living donor liver transplant.The grafted hepatic artery was first anastomosed to the recipient’s right hepatic artery stump.However,the arterial pulse immediately weakened.Although a new anastomosis was performed using the right gastroepiploic artery,the patient’s arterial pulse rate remained poor.We attempted angiographic intervention immediately after the operation;it showed diffuse arterial vasospasms like‘beads on a string’.We attempted continuous infusion of lipo-PGE1 overnight via an intra-arterial catheter.The next day,arterial flow improved without any spasms or strictures.The patient had no additional arterial complications or related sequelae at the time of writing,1-year post-liver transplantation.CONCLUSION Angiographic evaluation is helpful in cases of repetitive arterial obstruction,and intra-arterial infusion of lipo-PGE1 may be effective in treating diffuse arterial spasms.

Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

Protective effects of prostaglandin E1 on hepatocytes

INTRODUCTION E Numerous studies have demonstrated the protective action of prostaglandin E1(PGE1) on experimental animal models of liver injury and on patients with

Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations

BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS). Crohn's disease(CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD.AIM To examine whether prostaglandin E major urinary metabolites(PGE-MUM) can serve as a biomarker to distinguish CEAS from CD.METHODS This was a transactional study of 20 patients with CEAS and 98 patients with CD.CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1. We measured the concentration of PGEMUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC) curve analysis.RESULTS Twenty Japanese patients with CEAS and 98 patients with CD were enrolled.PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval(CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% specificity.CONCLUSION PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.

Prostaglandin E_1 in conjunction with high doses of vitamin B_(12) improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve conduction velocity of the median nerve and the common peroneal nerve were determined using an electromyogram electronic stimulator （Neuropack-11, Nihon Kohden, Japan）. RESULTS： The motor nerve and sensory nerve conduction velocities of the median nerve and the common peroneal nerve were significantly faster after treatment compared to before treatment in all 3 groups （P 〈 0.05q）.01）. Compared with the control group, the motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 low-dose treated group and in the vitamin B12 high-dose treated group （P 〈 0.01）. The motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 high-dose treated group compared to the vitamin B12 low-dose treated group （P 〈 0.05）. CONCLUSION： Prostaglandin E1, in conjunction with vitamin B12, can improve neural functional states and speed up peripheral motor nerve and sensory nerve conduction velocity in diabetic peripheral neuropathy. In addition, better effects are achieved using prostaglandin E1 in conjunction with high doses of vitamin B 12.

Effects of Prostaglandins and Leukotrienes on Hypoxic Pulmonary Vasoconstriction in Rats

To investigate the effects of prostaglandins (PGs) and leukotrienes (LTs) on hypoxic pulmonary vasoconstriction (HPV), in vivo rats experiment and in vitro perfused lung experiment were conducted. The effect of hypoxia on hemodynamics, concentrations of TXB 2 and 6 keto PGF 1α in serum and lung tissue during hypoxia and effects of PGs and LTs on HPV were observed. The results showed that pulmonary arterial pressure (P pa ) and pulmonary vascular resistance were increased during hypoxia, but cardiac output and systemic arterial pressure were decreased. There were increases of the concentrations of TXB 2 and 6 keto PGF 1α and their ratio in serum and lung tissue during hypoxia. After use of cyclooxygenase inhibitor (indomethacin) in vivo and in vitro , HPV was augmented respectively, but after use of lipoxygenase inhibitor (diethylcorbamazine) or leukotriene receptor blocker (LY 171883), HPV was attenuated. It was suggested that LTs mediated pulmonary vasoconstriction, PGs inhibited pulmonary vasoconstriction and they played a modulating role during hypoxia.

Effectiveness of 0.1% topical salicylic acid on blepharoconjunctivitis affecting glaucoma patients treated with topical prostaglandin analogues:a prospective randomized trial

AIM: To evaluate the efficacy of 0.1% topical salicylic acid（TSA） to treat iatrogenic chronic blepharoconjunctivitis in patients with primary open angle glaucoma（POAG）, treated with topical prostaglandin analogues（TPAs）.METHODS: Totally 60 patients were randomly distributed into 3 equal size groups, two of which treated with 0.1% TSA（OMKASA;） and 0.1% topical clobetasone butyrate（TCB; VISUCLOBEN;） respectively, and one consisting of untreated controls. The parameters taken into account at baseline（T0） and after 30 d（T1） of therapy were: conjunctival hyperemia, lacrimal function tests [Schirmer I test and break up time（BUT）] and intraocular pressure（IOP）.RESULTS: Conjunctival hyperemia showed a substantial improvement in both treated groups（P<0.001） but not among controls. Similarly, lacrimal function tests displayed an improvement of Schirmer I test in both treated groups（P<0.05） and an extension of BUT only in the group treated with 0.1% TSA（P<0.05）. The IOP increase was statistically significant only in those patients treated with 0.1% TCB（P<0.001）.CONCLUSION: The 0.1% TSA has proved to be an effective anti-inflammatory treatment of blepharoconjunctivitis affecting glaucoma patients on therapy with TPAs, leading to a sizeable decrease of inflammation as well as both quantitative and qualitative improvement of tear film. Furthermore, differently from 0.1% TCB, it does not induce any significant IOP increase.

Effect of Lipo-prostaglandin E_1 on Mesangial Proliferative Glomerulonephritis in Rats

Summary： The antinephritic effect of lipo-prostaglandin E1. prostaglandin E1 incorporated in lipid mierospheres was investigated using an experimental model of mesangial proliferative glomerulonephritis （MsPGN）. Twenty-two female rats were randomly divided into nephritic group （N, n=6）, lipo-prostaglandin E1 treated group （NL, n=8） and control group （C, n=6）. Lipo-prostaglandin E1 was given intravenously at 40 μg·kg^-1·d^-1 from the 6th week to the 8th week. Twenty-four h urinary protein contents and blood ereatinine （Cr） were determined and the pathological changes were observed in the experiment. The expression of proliferating cell nuclear antigen （PCNA）, extraeellular matrix （fibroneetin, FN; collagen type Ⅳ , Col Ⅳ ） and transforming growth factor β1 （TGFβ1） was detected by using immunohistoehemistry. The results showed that lipo-prostaglandin E1 significantly inhibited the glomerular histopathologieal changes as well as the elevation of plasma Cr （P〈0.05）. The overexpression of PCNA, FN, Col Ⅳ and TGFβ1 were also obviously inhibited in group NL as compared with the group N （P〈0.01）. It was suggested that lipo-prostaglandin E1 could improve renal function, inhibit the proliferation of glomerular cells and reduce the deposition of extraeellular matrix, which may be related to the down-regulation of the TGFβ1 expression.

Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis

BACKGROUND: Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type Ⅰ and Ⅲ collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis. METHODS: Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 μg/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining. RESULTS: Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related α-SMA and thecontent of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of α-SMA around the hepatic sinusoids (P【0.01). The contents of type Ⅰ and Ⅲ collagens were significantly attenuated. The ratio of staining area to the whole field (10×3.3) under a polarized light microscope in the untreated and treated groups was 37.25±9.71 vs. 13.38±4.24 (P【0.01) and 9.66±3.52 vs. 6.23±1.81 (P【0.05), respectively. CONCLUSIONS: Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at least in part by inhibiting the activation of HSCs.

Effects of prostaglandin E combined with continuous renal replacement therapy on septic acute kidney injury

BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.

Lonicera japonica-induced inhibition of interleukin-1 beta thermogenesis and E-type prostaglandin receptor-3 expression in the preoptic area of rabbits

BACKGROUND： It has been shown that interleukin-1β（IL-1β） can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2, which binds with receptors of the thermo-sensitive hypothalamic neurons. Lonicera japonica is one of the medicinal plants used widely in Asia for its antipyretic properties. However, these mechanisms have not yet been intensively studied. OBJECTIVE： To investigate the antipyretic effect and mechanisms of Lonicera japonica on IL-1β- induced febrile New Zealand rabbits by observing expression changes of E-type prostaglandin receptor-3 （EP3） mRNA in the preoptic anterior hypothalamus （POAH）. DESIGN： A randomized controlled study. SETTING： Electrophysiological Laboratory at the Department of Pathophysiology, Medical College of Jinan University; Department of Orthopaedics, First Hospital Affiliated to Medical College of Jinan University. MATERIALS： The experiment was performed from April to December 2005, using a total of 32 New Zealand white rabbits of both sexes, weighing 1.5 2.0 kg. All the animal experiments were performed according to the internationally accepted ethical guidelines. Lonicera japonica injection was purchased from Huanghe pharmaceutical factory of Xi＇an, China. IL-1βwas purchased from Sigma, USA. METHODS： A total of 32 rabbits were divided randomly into four groups： ① Normal saline （NS） control group;② Lonicerajaponica treatment group; ③ IL-1βtreatment group; and ④Lonicerajaponica plus IL-1βtreatment group. In the first 3 groups, the rabbits were given separate intravenous （i.v.） injections of l mL NS, l mL Lonicera japonica, and 100 ng IL-l β （dissolved in 0.9% NS without pyrogen）. In the Lonicerajaponica plus IL-1βgroup each rabbit was given i.v. injections of l mL NS and, 30 minutes later, 100 ng IL-1 β. MAIN OUTCOME MEASURES： Colonic temperature of each rabbit was measured at 0, 10, 20, 30, 40, 50, 60, and 70 minutes after injection and the maximum temperature rise （ A T） and the temperature response index after l hour （TRII） was calculated. Subsequently, in situ hybridization （ISH） was done with an ISH kit, EP3 mRNA expression in the POAH of all groups was measured （number of positive cells and average gray scale value）. RESULTS： A total of 32 rabbits were included in the result analysis, without any loss, （i） A T and TRII： there was no significant difference between the Lonicera japonica group and NS group （P 〉 0.05）. The IL-1β group was significantly greater compared to NS group （P 〈 0.01）. The Lonicera japonica plus IL-1β group was significantly less than the IL-1β group （P 〈 0.05）. ② In the NS and Lonicera japonica groups, the EP3 mRNA expression was negative （no coloration） or only weakly positive （only a few brown yellow particles in the cytoplasm cells could not be identified）. The number of positive cells and the average gray scale value were not significantly different between the two groups （P 〉 0.05）. In the IL-1β group, the number of positive cells was remarkably higher and the average gray scale value was lower than the NS group （P 〈 0.0 l）. In the Lonicera japonica plus IL-1β group, the number of positive cells was significantly less than the IL-1β group （P 〈 0.05）. However, the average gray scale value was greater than the IL-1β group （P 〈 0.05）. CONCLUSION： Lonicera japonica has obvious antipyretic effects on IL-1β-induced febrile rabbits and acts by inhibiting expression of EP3 mRNA in the POAH.

Protective effects of prostaglandin E1 perfusion againstspinal cord ischemia-reperfusion injury in a rabbit model

BACKGROUND： Prostaglandin E1 （PGE1） is known to be protective in ischemia-reperfusion of heart, lung,renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE： To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING： Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS： Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used： prostaglandin E1 injectable powder,as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS： We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 （100 ng/kg/min）. MAIN OUTCOME MEASURES： The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS： All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group （P 〈 0.05）. The scores of hind limb functions were greater in the experimental group after 12, 24, and 48 hours （P 〈 0.01）. CONCLUSION： Perfusion of PGE1 reduced the amount of neuronal damage in the spinal cord ischemia-reperfusion injury rabbit model. These results correlated with increased numbers large motor neurons in the ventral horn of the spinal cord, as well as improved hind limb function.

Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy

AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs （PGAs） monotherapy. METHODS： After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials （RCTs） comparing the fixed combination of PGAs/timolol therapy （FCs） and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal lOP, percentage of participants whose lOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS： After six-month medical intervention, the mean diurnal lOP of FCs was lower than PGAs （MD -1.14, 95% CI -1.82 to -0.46, P=0.001）; the percentage of target lOP achieving between FCs and PGAs showed no significant difference （RR 1.18, 95% Cl 0.97 to 1.43, P=0.10）. No statistically significant differences of the incidence of hyperemia （RR 0.67, 95% CI 0.45 to 1.01, p=0.06） and eye irritation （RR 1.20, 95% CI 0.95 to 1.51, P=0.12） between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects （central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% Cl -0.02 to 0.00, P=0.23）. The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION： The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering lOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.

INHIBITORY EFFECT OF ELECTROACUPUNCTURE ON FEVER INDUCED BY LIPOPOLYSACCHARIDE, INTERLEUKIN-1βAND PROSTAGLANDIN E_2 IN RATS

The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulation output; voltage intensity, 1 to 4 V; frequency, 1 Hz) was applied to bilateral equvalent Quchi (LI 11 ) acupoints for 30 min. Intraperitoneal injection of LPS (0111: B 4) at a single dose of 100 μg/kg caused high rectal temperature in rats, which was remarably sup pressed by EA either given simultaneously or 2 h after LPS injection. No difference in reduction of fever was found between two groups of rats treated by EA at different times. The rats that received adIninistration of hrIL-1β(2ng) or PGE2(3μg) into the prooptic area (POA) developed the acute and high fevers. The temperature in both cases was significantly decreased after EA stimulation. EA also partially inhibited the fever caused by intravenous injection of 0. 5μg/kg IL-1β. The they temperature increased within 1℃ in the rats that got intravenous injection of PGE2 (1. 5mg/kg), and EA did not present strong inhibitory effect on it. The present results demonstrate that EA possesses an antipyretic effect in rats and suggest that which may attribute to the suppression of the actions of IL-1β and/or PGE2 in the development of fever.

The effect of prostaglandin E_1 on recovery of early renal graft functions after transplantation

Objective To investigate the effect of prostaglandin E1 (PGE1) on recovery of early renal graft functions after transplantation. Methods One hundred and seven patients after renal transplantation were allocated in the treated group, and treated by conventional treatment with injection of 10 μg prostaglandin E1 additionally twice a day for 14 days. And eighty-eight patients who received conventional treatment alone after renal transplantation at the corresponding period were allocated in the control group. Indexes of the two groups, including incidence of delayed graft function and acute rejection reaction, volume of urine, serum certaintie (SCr), endogenous certainties clearance rate (CCr), the blood flow resistance in graft as well as blood viscosity (BV), and platelet aggregation rate (PAR), were determined. Results The urinary volume and endogenous certainties clearance rate of the treated group were significantly higher, but the level of SCr, incidence of renal function recovery retardation, BV, PAR and blood flow resistance in graft were significantly lower than those of the control group (P<0.05). The difference of incidence of acute rejection reaction between the two groups was insignificant (P>0.05). Conclusion Prostaglandin E1 can improve blood microcirculation and decrease the incidence of renal function recovery retardation. These effects are helpful for recovery of renal function after renal transplantation.

The Application of Prostaglandin E_1 Indirect Portal Vein Angiography and Color Doppler Ultrasound in Patients with Post－deva

The selection of proper treatment is based on identification of the causes of massive hemorrhage of gastrointestinal tract after pericardial devascularization.The combined use of prostaglandin E1 indirect portal vein angiography, DSA of celiac artery and color Doppler can provide detailed information about portal vein system,including the presence of embolism, spongioid changes and devasculization of left gastric vein and left gastric artery and the direction of blood flow. If these techniques failed to reveal the causes of digestive tract bleeding, the endoscopy may show lesions of gastric mucosa, which could be accountable for the bleeding.