Polyunsaturated fatty acids alter the formation of lipid droplets and eicosanoid production in Leishmania promastigotes

BACKGROUND The knowledge about eicosanoid metabolism and lipid droplet (LD) formation in the Leishmania is very limited and new approaches are needed to identify which bioactive molecules are produced of them. OBJECTIVES Herein, we compared LDs and eicosanoids biogenesis in distinct Leishmania species which are etiologic agents of different clinical forms of leishmaniasis. METHODS For this, promastigotes of Leishmania amazonensis, L. braziliensis and L. infantum were stimulated with polyunsaturated fatty acids (PUFA) and LD and eicosanoid production was evaluated. We also compared mutations in structural models of human-like cyclooxygenase-2 (GP63) and prostaglandin F synthase (PGFS) proteins, as well as the levels of these enzymes in parasite cell extracts. FINDINGS PUFAs modulate the LD formation in L. braziliensis and L. infantum. Leishmania spp with equivalent tissue tropism had same protein mutations in GP63 and PGFS. No differences in GP63 production were observed among Leishmania spp, however PGFS production increased during the parasite differentiation. Stimulation with arachidonic acid resulted in elevated production of hydroxyeicosatetraenoic acids compared to prostaglandins. MAIN CONCLUSIONS Our data suggest LD formation and eicosanoid production are distinctly modulated by PUFAS dependent of Leishmania species. In addition, eicosanoid-enzyme mutations are more similar between Leishmania species with same host tropism.

Use of protein kinase C and phospholipase A2 inhibitors in bovine endometrial cells treated with estradiol and calcium ionophore / Uso de inibidores de proteína quinase C e fosfolipase A2 em células endometriais bovinas tratadas com estradiol e ionóforo de cálcio

The release of endometrial prostaglandin-F2α (PGF2α) in bovine females can be induced in vivo by estradiol (E2). However, its role in this mechanism has not been clarified. We hypothesized that E2 stimulates the activity and abundance of protein kinase C (PKC) and phospholipase A2 (PLA2). Our objective in this study was to analyze the effects of PKC and PLA2 inhibitors on PGF2α synthesis induced by E2 and calcium ionophore (CI) in bovine endometrial cells (BEND cells; Experiment 1). Additionally, we evaluated the abundance of PKC and PLA2 in endometrial explants of cows treated or not with E2 17 days after estrus (D17, D0 = estrus; Experiment 2). In Experiment 1, BEND cells were submitted to a PKC inhibitor (10 µM of C25H24N4O2; bisindolylmaleimide I, or BIS I), a PLA2 inhibitor (20 µM of arachydoniltrifluoromethane or AACOCF3), or none. The BEND cells were subsequently treated with E2 and CI, and PGF2α concentrations were measured in the culture medium through radioimmunoassay. For DIF-12 (PGF2α concentration 12 h after treatment subtracted from PGF2α concentration at hour 0), no PKC inhibitor effect was observed (P= 0.2709). However, DIF-12 was lower (P < 0.05) for groups treated with the PLA2 inhibitor and PLA2 inhibitor + CI + E2 groups than the control and CI + E2 groups. Thus, AACOCF3 was an efficient PLA2 inhibitor in the BEND cells culture system, and E2 did not stimulate the synthesis of PKC and PLA2. In Experiment 2, cyclic Nellore heifers received none (n = 5) or 3 mg (n = 6) of 17ß-E2 on D17 and were slaughtered 2 h after administration. The abundance of PKC and PLA2 in the endometrial tissue was evaluated using Western blotting analysis. No E2 effect was observed on PKC (P = 0.08) and PLA2 (P = 0.56). We concluded that E2 did not stimulate the activity and abundance of PKC and PLA2.(AU)

A liberação endometrial de prostaglandina-F2α (PGF2α) em fêmeas bovinas pode ser induzida in vivo pelo estradiol (E2). Entretanto o seu mecanismo de ação ainda não foi bem esclarecido. Nossa hipótese é que o E2 estimula a atividade e a abundância da proteína quinase C (PKC) e da fosfolipase A2 (PLA2). Nosso objetivo com este estudo foi analizar os efeitos de inibidores de PKC e PLA2 na síntese de PGF2α induzida por E2 e ionóforo de cálcio (CI) em células endometriais bovinas (células BEND; Experimento 1). Adicionalmente, nós avaliamos a abundância de PKC e PLA2 em explantes endometriais de vacas tratadas com ou sem E2 17 dias após o estro (D17, D0 = estro; Experimento 2). No Experimento 1, células BEND foram submetidas ao inibidor de PKC (10 µM de C25H24N4O2; bisindolylmaleimide I, ou BIS I), e ao inibidor de PLA2 (20 µM de arachydoniltrifluoromethane ou AACOCF3) ou a nenhum inibidor. As células BEND foram subsequentemente tratadas com E2 e CI e concentrações de PGF2α foram mensuradas no meio de cultura por radioimunoenssaio. Para DIF-12 (concentração de PGF2α 12 horas depois do tratamento, subtraída da concentração de PGF2α na hora 0), não foi observado efeito do inibidor de PKC (P = 0.2709). Entretanto DIF-12 foi menor (P < 0.05) nos grupos tratados com inibidor de PLA2 e inibidor de PLA2 + CI + E2 quando comparados com o grupo controle e o grupo CI + E2. O AACOCF3 foi um eficiente inibidor de PLA2 em sistema de cultura de células BEND e o E2 não estimulou a síntese de PKC e PLA2. No Experimento 2, novilhas Nelore cíclicas receberam 3 mg de 17ß-E2 (n = 6) ou nenhum tratamento (n = 5) no D17 e foram abatidas duas horas depois da administração dos tratamentos. A quantidade de PKC and PLA2 no tecido endometrial foi avaliada pela técnica de Western Blotting. Não foi observado efeito do E2 sobre a PKC (P= 0.08) e nem sobre a PLA2 (P= 0.56). Conclui-se que o E2 não estimulou a atividade e abundância de PKC e PLA2.(AU)

Effect and mechanism of total glucosides of Paeoniae Radix Alba on combined model of chemical liver injury and liver yin deficiency syndrome in rats / 中草药

Objective: Based on the establishment of experimental model of liver yin deficiency syndrome, the effects of total glucosides of Paeoniae Radix Alba on the syndrome model of liver yin deficiency syndrome in rats with chemical liver injury were studied. Methods: SPF male Sprague-Dawley rats weighing (200 ± 20) g, after adaptive feeding, were randomly divided into control group, model group, Yi Guan Jian group, and total glycosides of Paeoniae Radix Alba group. Except the control group, the rats in the other groups were intraperitoneally injected with 20% CCl4 olive oil solution, and then ig treated with Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma and Cinnamomi Cortex to establish liver yin deficiency syndrome model. The Yi Guan Jian group and the total glucoside of Paeoniae Radix Alba group were administered at the same time, once a day for 6 weeks. After 6 weeks, the body weight and anal temperature of the rats were measured, and the general state was observed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), 6-keto-prostaglandin F1α (6-keto-PGF1α), plasma thrombosis content of B2 (TXB2), laminin (LN) and hyaluronic acid (HA) were measured, and the activity of liver tissue interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF-α) were measured. The expression levels of phosphatidylinositol kinase (PI3k) mRNA, protein kinase B (Akt) mRNA and protein were determined and livers were taken for pathological examination of HE. Results: Compared with the model group, the scores of the total glucosides of Paeoniae Radix Alba group were significantly increased (P < 0.05), the body weight was significantly increased (P < 0.05), and the serum ALT and AST levels were significantly decreased (P < 0.01, 0.001). The cAMP/cGMP ratio was increased significantly (P < 0.01). The LN and HA of the liver tissue of the total glycosides group were significantly decreased (P < 0.05, 0.001). The content of TNF-α and IL-6 was decreased significantly (P < 0.001), the expression level of Akt protein was decreased significantly (P < 0.05), the expression of PI3K and Akt mRNA was decreased significantly (P < 0.05, 0.001), and liver pathological sections were improved. Conclusion: The extract of Paeoniae Radix Alba has the effect of protecting liver injury with yin deficiency syndrome, which may be the material basis of supplement liver yin of Paeoniae Radix Alba. Its mechanism of action may be related to anti-inflammatory, alleviate microcirculatory disorders, and regulate the balance of cytokines IL-6 and IL-10 by inhibiting the PI3K-Akt pathway.

Anti-placental growth factor antibody ameliorates hyperoxia-mediated impairment of lung development in neonatal rats

This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia+Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia+anti-PGF groups, respectively. Our results revealed significant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia+Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment significantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression significantly increased TNF-α and Il-6 levels in the bronchoalveolar lavage (BAL) fluid of the Normoxia+Ad-PGF and Hyperoxia groups. However, their levels were significantly reduced in the BAL fluid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment significantly increased the expression of the angiogenesis marker, CD34. However, its expression was significantly decreased upon administration of anti-PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.

Investigation of vascular endothelial function in active polyarticular juvenile idiopathic arthritis / 中国实用儿科杂志

OBJECTIVE: To investigate the changes of vascular endothelial function in children with active polyarticular juvenile idiopathic arthritis(JIA)and the effects of oxidative stress and lipid metabolism on endothelial function.METHODS: Totally 42 children with active polyarticular JIA were divided into rheumatoid factor(RF)positive group and RF negative group,and 23 healthy children were randomly selected as normal control group. Brachial artery flow-mediated dilation(FMD),carotid intima-media thickness(cIMT),lipid profile and oxidative stress were measured and compared among these groups. RESULTS: Brachial artery FMD in the RF positive and the RF negative groups were significantly lower than those in the control group,especially in RF positive patients(P<0.05,respectively). There were no significant differences in c IMT.Serum TG level was significantly higher(P<0.05),while HDL-C level was significantly lower(P<0.05)in the RF-positive group compared with the control group. Serum 8-iso-PGF2α level was significantly higher(P<0.001)in the RF-positive group compared with the control group. However,significant increase in 8-iso-PGF2α level was observed in the RF negative group(P<0.01). Similarly,8-iso-PGF2α level increased more significantly in RF positive group compared with RF negative group(P<0.05). Brachial artery FMD in polyarticular JIA was negatively associated with serum 8-iso-PGF2α(r=-0.54,P<0.01). CONCLUSION: Vascular endothelial dysfunction exists in the active polyarticular JIA,especially in RF-positive patients. Increasing oxidative stress may impair the endothelial function;however,the impact of dyslipidemia on endothelial function is not clear in polyarticular JIA.

Endometrial prostaglandin F2α in vitro production and its modulation regarding dominant follicle position in cattle / Produção in vitro de PGF F2α endometrial e sua modulação referente ao folículo dominante em bovinos

Prostaglandin F2α (PGF2α) determines luteolysis in cattle, and the ability to manipulate its endogenous synthesis is indispensible for large-scale animal breeding. Estradiol (E2) and progesterone (P4) modulate several molecular pathways in endometrial cells, including the synthesis of PGF2α; however, its specific mechanisms are still not totally known. This study investigated the production in vitro and possible modulation of endometrial PGF2α due to a local effect of endogenous E2 in the ipsilateral uterine horn (UH) containing the dominant follicle (DF) or from P4 in ipsilateral horn containing the corpus luteum (CL). The PGF2α stimulators oxytocin (OT) and phorbol 12,13-dibutyrate (PDBu) were incubated with endometrial explants, and PGF2α content was measured. For that, cycling cows were synchronized, the development of DF and CL was examined by ultrasonography and on the seventh day of the estrous cycle, endometrial explants were collected and cultured in medium supplemented with 10-6 M PDBu or 10-6 M OT or non-supplemented. Media samples were collected immediately after treatment and 60 min later. Radioimmunoassay showed that the PGF2α content of the UH ipsilateral to the DF was 49% less than that of the contralateral UH (8.22 ± 0.95 vs. 12.24 ± 0.95 pg/mL/mg tissue, respectively; P < 0.01). However, the PGF2α levels did not differ between the UHs as a function of the CL position (9.46 ± 0.95 vs. 11 ± 0.95 pg/mL/mg; P > 0.05). The cellular stimulators promoted an increase in PGF2α synthesis (P < 0.02), and the effects differed among the animals (P < 0.04). The PGF2a production was higher in the explants treated with PDBu rather than OT (13.68 ± 1.16 vs. 10.01 ± 1.16 pg/mL/mg tissue, respectively; P < 0.05). In conclusion, PGF2α synthesis is modulated by the presence of the DF (local E2) but not the CL (local P4), and both PDBu and OT stimulated PGF2a synthesis.(AU)

A prostaglandina F2α (PGF2α) determina a luteólise em bovinos. A capacidade de manipular sua síntese endógena é indispensável para a produção animal em grande escala. O estradiol (E2) e a progesterona (P4) modulam diversas vias moleculares das células endometriais, incluindo a síntese de PGF2α; no entanto, pouco se sabe sobre seus mecanismos específicos. Este trabalho investigou a produção in vitro e a possível modulação da PGF2α endometrial devido a um efeito local do E2 endógeno no corno uterino ipsilateral ao folículo dominante (FD) ou da P4 no corno ipsilateral ao corpo lúteo (CL). Os estimuladores de PGF2α oxitocina (OT) e 12,23-dibutirato de forbol (PDBu) foram incubados com explantes endometriais, e o conteúdo de PGF2α foi mensurado. Para tal, vacas cíclicas foram sincronizadas, o desenvolvimento de FD e CL foi examinado por ultrassonografia, e no 17º dia do ciclo estral os explantes endometriais foram coletados e cultivados em meio ou suplementados com PDBu 10-6M ou 10-6M OT. As amostras de meio foram coletadas imediatamente após o tratamento e sessenta minutos depois. O radioimunoensaio mostrou que o conteúdo de PGF2α do corno ipsilateral ao FD foi 49% menor que o do corno contralateral (8,22 ± 0,95 vs. 12,24 ± 0,95 pg/mL/mg de tecido, respectivamente, P < 0,01). No entanto, os níveis de PGF2α não diferiram entre os cornos em função da posição do CL (9,46 ± 0,95 versus 11 ± 0,95 pg/mL/mg; P > 0,05). Os estimuladores celulares promoveram um aumento na síntese de PGF2α (P < 0,02), e os efeitos diferiram entre os animais (P < 0,04). A produção de PGF2α foi maior nos explantes tratados com PDBu em comparação à OT (13,68 ± 1,16 versus 10,01 ± 1,16 pg/mL/mg de tecido, respectivamente, P < 0,05). A conclusão obtida foi que a síntese de PGF2α é: modulada pela presença do FD (E2 local), mas não do CL (P4 local); e estimulada por PDBu e OT.(AU)

Separation and simultaneous quantitation of PGF2 and its epimer 8--PGF2 using modifier-assisted differential mobility spectrometry tandem mass spectrometry

Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS-MS/MS method to separate and simultaneously quantify epimers, taking PGF2 and its 8-epimer, 8--PGF2, as an example. Good accuracy and precision were achieved in the range of 10-500 ng/mL with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.

Effects of the Acupoint Catgut Embedding on Nerve-Endocrine-Immune Network in Dysmenorrhea Rats / 针刺研究

OBJECTIVE: To explore the underlying mechanism of acupoint catgut embedding in improving primary dysme-norrhea (PD) in rats based on functional activities of the neuro-endocrine-immune (NEI) network. METHODS: Forty female rats were equally randomized into blank control, PD model, medication, and acupoint catgut embedding groups. The PD model was established by subcutaneous injection of estradiol benzoate (0.5 mg/rat on the 1st and 10th d, and 0.2 mg/rat from 2nd to 9th d) and oxytocin (2 U/rat, i．p.). Rats of the medication group were treated by intragastric perfusion of fenbid (0.8 mL/rat, 125 mg/100 mL), once daily for 10 days. The catgut embedding was applied to bilateral "Ciliao" (BL 32), "Sanyinjiao" (SP 6) and "Guanyuan" (CV 4) before modeling. The body writhing times in 30 minutes were recorded, plasma β-endorphin(β-EP) content, and prostaglandin E 2 (PGE2) and prostaglandin F 2 α (PGF2α) contents in the uterus tissue were assayed using ELISA, and the activity of natural killer cell (NK cell) in the spleen tissue was detected using 3-(4，5-dimethyl-2-thiazolyl)-2，5-diphenyl-2-H-tetrazolium bromide (MTT) method after isolation and co-culture with K 562 cells. RESULTS: The body writhing times were no-tably more in the model group than in the control group (P0.05). CONCLUSION: The acupoint catgut embedding has a significant efficacy in relieving PD in rats, which may be related to its effect in up-regulating plasma β-EP, uterus PGE2 contents and splenic NK cell activity and in down-regulating uterus PGF2α level.

Therapeutic Observation of Regulating Spleen-stomach Needling for Type 2 Diabetic Foot / 上海针灸杂志

Objective To observe the clinical efficacy of needling method of regulating spleen-stomach in treating early-stage type 2 diabetic foot (DF).Method A hundred patients with early-stage type 2 DF were randomized into a treatment group and a control group,50 cases each.The two groups both received conventional treatment for diabetes.In addition,the treatment group was intervened by needling method of regulating spleen-stomach;the control group was given oral administration of Pancreatic kininogenase enteric-coated tablets.After 6-week treatment,the changes in fasting blood glucose (FBG),2-hour postprandial blood glucose (P2hBG),serum total cholesterol (TC),triglyceride (TG),6-keto-PGF1α and thromboxane B2 (TXB2) contents were observed.The clinical efficacies of the two groups were also compared.Result The total effective rate was 91.8％ in the treatment group versus 75.5％ in the control group,and the between-group difference was statistically significant (P＜0.05).The levels of FBG,P2hBG,TC,TG,6-keto-PGF1α and TXB2 were significantly changed after the intervention in the two groups (P＜0.01,P＜0.05).The treatment group was significantly different from the control group in comparing each parameter after the intervention (P＜0.01,P＜0.05).Conclusion Needling method of regulating spleen-stomach is an effective method in treating early-stage type 2 DF,and can improve the progressive injury induced by abnormal glucose metabolism.

Kaempferol inhibited VEGF and PGF expression and in vitro angiogenesis of HRECs under diabetic-like environment

Diabetic retinopathy (DR) is one of the common and specific microvascular complications of diabetes. This study aimed to investigate the anti-angiogenic effect of kaempferol and explore its underlying molecular mechanisms. The mRNA expression level of vascular endothelial growth factor (VEGF) and placenta growth factor (PGF) and the concentrations of secreted VEGF and PGF were measured by qTR-PCR and ELISA assay, respectively. Human retinal endothelial cells (HRECs) proliferation, migration, and sprouting were measured by CCK-8 and transwell, scratching wound, and tube formation assays, respectively. Protein levels were determined by western blot. High glucose (25 mM) increased the mRNA expression levels of VEGF and PGF as well as the concentrations of secreted VEGF and PGF in HRECs, which can be antagonized by kaempferol (25 µM). Kaempferol (5-25 µM) significantly suppressed cell proliferation, migration, migration distance and sprouting of HRECs under high glucose condition. The anti-angiogenic effect of kaempferol was mediated via downregulating the expression of PI3K and inhibiting the activation of Erk1/2, Src, and Akt1. This study indicates that kaempferol suppressed angiogenesis of HRECs via targeting VEGF and PGF to inhibit the activation of Src-Akt1-Erk1/2 signaling pathway. The results suggest that kaempferol may be a potential drug for better management of DR.

Impacts of Preeclampsia on the Brain of the Offspring / Impactos da pré-eclâmpsia no cérebro de nascituros

Abstract Preeclampsia (PE) is a significant gestational disorder that causes complications in 3- 5% of all human pregnancies. Apart from the immediate risks and complications for mother and fetus, both additionally carry elevated lifelong risks for specific complications. Offspring of PE pregnancies (PE-F1) have higher risks for hypertension, stroke and cognitive impairment compared with well-matched offspring (F1) fromuncomplicated pregnancies. Prior to the clinical onset of PE, placental angiokines secreted into the maternal plasma are deviated. In many PE patients this includes deficits in placental growth factor (PGF). Our laboratory found that mice genetically-deleted for PGF (PGF - / -) have altered cerebrovascular and brain neurological development detectable from midgestation to adulthood. We hypothesized that the PGF deficits seen in human PE, deviate fetal cerebrovascular and neurological development in a manner that impairs cognitive functions and elevates stroke risk. Here we summarize the initial analytical outcomes from a pilot study of 8-10 year old male and female PE-F1s and matched controls. Our studies were the first to report magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and functional brain region assessment by eyemovement control and clinical psychometric testing in PE-F1s. Further studies in larger cohorts are essential to define whether there are image-based biomarkers that describe unique anatomical features in PE-F1 brains.

Resumo A pré-eclampsia (PE) é importante doença gravídica complicando 3-5% de todas as gestações humanas. Além dos riscos imediatos e complicações para a mãe e o feto, a PE associa-se a outros riscos materno-fetais elevados em longo prazo. Nascituros de gestações complicadas por PE (PE-F1) apresentam maiores riscos de desenvolver hipertensão, acidente vascular cerebral e disfunção cognitiva em comparação com prole (F1) de gestações sem complicações. Antes do aparecimento clínico da PE, angiocitocinas placentárias secretadas no plasma materno apresentam-se alteradas. Em muitos pacientes com PE, isso inclui valores plasmáticos reduzidos de Fator de Crescimento Placentário (PGF). Nosso laboratório identificou que camundongos geneticamente não produtores de PGF (PGF- / - ) apresentam alterações vasculares e de desenvolvimento cerebral detectáveis do período gestacional à idade adulta. Nossa hipótese é que os déficits de PGF identificados em mulheres que desenvolveram PE podem desviar o desenvolvimento neurológico e vascular cerebral fetal, de maneira a prejudicar funções cognitivas, elevando o risco de AVC. Aqui resumimos os resultados analíticos iniciais de um estudo piloto comcrianças do sexomasculino e feminino de 8- 10 anos de idade nascidas de mães que tiveram PE (PE-F1s) comparadas com crianças controle pareadas por idade e sexo. Nossos estudos são os primeiros a relatar a ressonância magnética (RNM), a angiorressonância e a avaliação funcional do cérebro pelo controle de movimento dos olhos e pelo teste clínico psicotécnico em PE-F1s. Estudos adicionais em coortes maiores são essenciais para definir se há biomarcadores com base em imagens que possam descrever características anatômicas únicas em cérebros de crianças PE-F1.

Prophylactic Intramuscular PGF2  Versus Intravenous Methylergometrine For Prevention Of Atonic PPH In High Risk Pregnant Women.

To assess, evaluate and compare the safety and efficacy of i/m PGF2  125 mcg and i/v methylergometrine 0.2 mg during active management of third stage of labor in high risk pregnant women who are prone to develop atonic postpartum hemorrhage. The study was conducted on two hundred women prone to develop PPH with vertex presentation and spontaneous onset of labor at term. Slected cases were divided into two groups: Group I – Comprised of 100 women who were given 125 microgram of intramuscular 15 methyl PGF2  (Carboprost) at the time of delivery of anterior shoulder prophylactically. Group II – Comprised of 100 women who were given 0.2 milligrams of intravenous methylergometrine, at the time of delivery of anterior shoulder prophylactic ally. Tools of statistical analysis used were paired ‘t’ test , ‘Z’ test and mean ± SD. The mean duration of the third stage of labor after giving uterotonic drug was significantly shorter in Group I (3.50 ± 1.10 mins) as compared to Group II (5.15 ± 1.30 min) (p<0.001).The mean blood loss was significantly less in Group I (85 ± 30 ml) versus Group II (185 ± 40 ml) (p<0.0001).There was no statistical difference in mean haemoglobin concentration observed before and 48 hrs after delivery. The only significant side effect was diarrhoea in Group I. Prophylactic intramuscular PGF2  125 mcg is a better alternative to prophylactic intravenous methylergometrine 0.2 mg in high risk pregnant women who are prone to develop atonic PPH.

Inhibitory effects of Sanjie Zhentong capsule on primary mouse myometrial cells contraction induced by prostaglandin F2α / 中国药理学通报

Aim To investigate the effects of Sanjie Zhentong capsule on cultured mouse myometrial cell contraction induced by prostaglandin F2α( PGF2α) , and to elucidate the mechanism of Sanjie Zhentong capsule in treating dysmenorrheal. Methods Primary mouse myometrial cells were cultured and identified. Intracel-lular calcium ( [ Ca2+] i ) was monitored under a Flex-Station 3 Benchtop Multi-Modo Microplate Reader u-sing Calcium 6-QF. Myometrial cells were labeled to observe the changes of contraction. The expressions of calmodulin ( CaM ) , myosin light chain kinase ( ML-CK) , myosin light chain phosphorylation( p-MLC20 ) in mouse uterine smooth muscle cells ( USMCs ) were determined by immunofluorescence. Results Sanjie Zhentong capsule suppressed the intracellular[Ca2 + ]i inflow and reduced the areas of myometrial cells induced by PGF2α. Then it significantly decreased CaM and p-MLC20 levels. Conclusion Our results indicate that Sanjie Zhentong capsule has inhibitory effect on dysmenorrheal induced by PGF2α. Furthermore,its major mechanism may be related with the regulation of intracellular[ Ca2 + ]i inflow and the levels of CaM and p- MLC20.

Effects of different regimens of PGF2α treatment during postpartum on reproductive performance in dairy cows / Efeito de diferentes regimes de tratamento pós-parto com PGF2α sobre o desempenho reprodutivo de vacas leiteiras

The aim of this study was to evaluate the effects of early postpartum PGF2α treatment on reproductive performance in dairy cows synchronized with targeted breeding and natural mating after voluntary waiting period. In this experiment ,120 cows were assigned to three groups irrespective of presence or absence of luteal tissue. Cows in PG- 14 group were treated with PGF2α from day 14 postpartum, cows in PG-28 group were treated with PGF2α from day 28 postpartum and cows in PG-42 group were not treated with PGF2α until the end of voluntary waiting period (d 42). After day 42 postpartum, cows in three groups were treated with PGF2α within 14-day intervals until natural mating after voluntary waiting period. Recorded reproductive parameters included days to first heat, days to first mating, days open, service per conception, conception rate, percentage of repeat breeder animals and pregnancy loss. Early PGF2α treatment from day 14 postpartum significantly decreased days to first estrus (34.9 ± 0.74, P < 0.003), days to first mating (62.35 ± 1.53, P < 0.04), days open (117.23 ± 3.1, P < 0.001) and service per conception (1.9 ± 0.09, P < 0.02); and PG-14 group presented increased conception rate (52.5%, P < 0.05). The proportion of repeat breeder syndrome tended to be affected by treatment with PGF2α from day 14 postpartum. In conclusion, treatment of cows with PGF2α from day 14 postpartum improved reproductive performance.(AU)

O objetivo do presente trabalho foi avaliar os efeitos do tratamento pós-parto precoce com PGF2α sobre o desempenho reprodutivo de vacas leiteiras sincronizadas para reprodução controlada por monta natural após o período de espera voluntário. Neste experimento, 120 vacas foram distribuídas em três grupos independentes da presença ou ausência de corpo lúteo. Vacas no grupo PG-14 foram tratadas com PGF2α a partir do 14o dia pósparto, vacas do grupo PG-28 foram tratadas com PGF2α a partir do 28o dia pós-parto e as vacas do grupo PG-42 não foram tratadas com PGF2α até o final do período de espera voluntário (d42). Após o 42o dia pós-parto as vacas dos três grupos foram tratadas com PGF2α com intervalos de 14 dias até a monta natural após o período de espera voluntário. Os registros dos parâmetros reprodutivos incluíram: dias para o primeiro estro, dias para a primeira cobertura, dias em aberto, serviços por concepção, taxa de concepção, percentagem de animais repetidores de cios e as perdas de gestações. O tratamento precoce com PGF2α, a partir do 14o dia pós-parto reduziu significativamente os dias para o primeiro estro (34,9 ± 0,74, P < 0,003), dias para a primeira cobertura (62,35 ± 1,53, P < 0,04), dias em aberto (117,23 ± 3,1, P< 0,02); e o grupo PG-14 apresentou um acréscimo na taxa de concepção (52,5%, P < 0,05). A proporção da síndrome de vacas repetidoras de cios tendeu a ser afetada pelo tratamento com PGF2α a partir do 14o dia pós-parto. A conclusão obtida foi que o tratamento das vacas com PGF2α a partir do 14o dia pós-parto melhorou o desempenho reprodutivo dos animais.(AU)

Effect of Different Acupuncture Stimuli on Uterine Micro-circulation and Circulation-related Substances of Dysmenorrheal Rats with Cold Stagnation Syndrome / 中国中医药信息杂志

Objective To explore the effect of different acupuncture stimuli on uterine micro-circulation of dysmenorrheal rats with cold stagnation syndrome. Methods Totally 32 three-month old female SD rats in diestrus were randomly divided into saline control group, model group, A stimuli group, and B stimuli group, 8 rats in each group. Model group and treatment groups were given whole body freezing combined with estradiol benzoate injection method to establish models. A stimuli group was given deep puncture with manipulation, while B stimuli group was treated by shallow puncture without manipulation. Diameter of uterine capillary,micro-vessel, TXB2, and 6-keto-PGF1αlevels were observed in each group. Results Compared with the saline group, capillary diameter in model group was significantly reduced at 5, 10, 20, 30 min time point (P<0.01);micro-vascular diameter was significantly reduced at 5, 10, 20, 30, 40 min time point (P<0.01);plasma 6-keto-PGF1α levels decreased (P<0.01);TXB2/6-keto-PGF1αincreased significantly (P<0.01). Compared with model group, capillary diameter in A stimuli group enlarged at 5, 10, 20, 30 min time point (P<0.05), micro-vascular diameter dilated at 5, 10, 20, 30, 40 min time point (P <0.01), plasma 6-keto-PGF1α level increased (P <0.05), TXB2/6-keto-PGF1αdecreased significantly (P<0.05);micro-vascular diameter in B stimuli group dilated at 20, 30 min time point (P<0.05), plasma TXB2/6-keto-PGF1α decreased significantly (P<0.05). Compared with B stimuli group, capillary diameter in A stimuli group dilated at 5, 10, 20, 30 min time point (P<0.05) and micro-vascular diameter dilated at 5, 10, 20, 30, 40 min time point significantly (P<0.01). Conclusion Dysmenorrheal rats with cold stagnation syndrome show obvious disorder of the uterus micro-circulation and circulation related substances. Both A and B acupuncture stimuli improved uterus micro-circulation of dysmenorrheal rats with cold stagnation syndrome, and its mechanism may be related to the recovery the balance between TXB2 and 6-keto-PGF1α.

Effect of edaravone on inflammatory factors 6-keto-prostaglandin F1α, thromboxane B2, endothelial function, copeptin and N-terminal brain natriuretic peptide in patients with acute cerebral infarction / 中国生化药物杂志

Objective To investigate effect of edaravone on serum inflammatory factors, 6-keto-prostaglandin F1α(6-keto-PGF1α), thromboxane B2, endothelial function and serum copeptin and N-terminal brain natriuretic peptide (NT-proBNP) in patients with acute cerebral infarction.Methods From March 2013 to September 2014, 213 cases of acute cerebral infarction were selected in the hospital and randomly divided into control group (n=101) and observation group (n =112).Control group were given conventional symptomatic treatment, and observation group were given edaravone injection on the basis of control group.The serum inflammatory cytokines, 6-keto-PGF1α, thromboxane B2, endothelial function, serum copeptin, NT-proBNP and nerve function score and activities of daily living ( ADL) score were compared between two groups.Results Serum CRP, IL-8, IL-10 in observation group after treatment were significantly lower than control group (P<0.05).Plasma thromboxane B2 in observation group after treatment was significantly lower than control group (P<0.05).The levels of 6-keto-PGF1αwas significantly higher than control group (P<0.05).Serum copeptin and NT-proBNP levels in observation group after treatment were significantly lower than control group (P<0.05).Plasma ET-1 in observation group after treatment was significantly lower than control group ( P<0.05 ) , and plasma NO was significantly higher than the control ( P<0.05 ).Neurological function in observation group after treatment was significantly lower than control group (P<0.05), and ADL score was significantly higher (P<0.05). Conclusion The preliminary study shows that edaravone in treatment of acute cerebral infarction may be associated with decreasing serum inflammatory cytokines, increasing 6-keto-PGF1αand reducing thromboxane B2, improving endothelial function and reducing serum copeptin and N-terminal natriuretic peptide.

Effects of Prescription of Nourishing Blood and Stretching of Stoke on TXB2 and 6-Keto-PGF1αof Patients with Acute Ischemic Cerebrovascular Disease / 中国中医药信息杂志

Objective To investigate the effects of prescription of nourishing blood and stretching of stoke (PNBSS) on the levels of TXB2 and 6-Keto-PGF1αin serum of patients with acute ischemic cerebrovascular disease (AICD);To discuss its action mechanism in AICD treatment. Methods Ninety patients with AICD were randomly divided into trial group and control group, 45 cases in each group. The control group received western routine treatment, while the trail group received the western routine treatment plus PNBSS, one dose per day, for one week. Rating scale of neurologic deficit was employed to evaluate treatment effectiveness. Venous blood was collected before the treatment and on the 3rd and 7th days of treatment. Levels of TXB2 and 6-Keto-PGF1αin serum were detected respectively. Results The score of neurologic deficit of post-treatment in two groups apparently decreased compared with baseline (P<0.01), and score of neurologic deficit in trial group on 7th day was lower than that of control group (P<0.05). The total effective rate in trial group was 93.3%, which was apparently higher than that of control group (84.4%). The level of TXB2 in serum and ratio of TXB2/6-Keto-PGF1α (T/P) in two groups on 3rd and 7th days remarkably decreased compared with baseline (P<0.01), while the level of 6-Keto-PGF1α in two groups on 3rd and 7th days was higher than that of baseline (P<0.01). Meanwhile, the level of TXB2 and ratio of T/P in two groups on 7th day were apparently lower than that of 3rd day (P<0.01), and the level of 6-Keto-PGF1αon 7th day was higher than that of 3rd day (P<0.01). The level of TXB2 in serum and ratio of T/P on 3rd and 7th days in trial group were apparently lower than that of control group (P<0.01, P<0.05), while the level of 6-Keto-PGF1α on 3rd and 7th days in trial group was apparently higher than that of control group (P<0.01, P<0.05). Conclusion One of the mechanisms of PNBSS for AICD appears to inhibit overavtivity of thrombocyte, and regulate the misadjustment of ratio of T/P.

Correlation of Serum 8-iso-PGF2αLevel and the Severity of Neurological Deficits in Elderly Patients with Cerebral Infarction / 天津医药

Objective To investigate the relationship between the level of 8-iso-prostaglandin (8-iso-PG)F2αand the neural functional deficit in patients with acute cerebral infarction (ACI). Methods Sixty-seven ACI patients were se-lected in Neurological Department of Ganyu People’s Hospital. According to the age, these subjects were divided into two groups:the old group (≥60 years, n=37) and middle-young group (<60 years, n=30). Thirty healthy subjects were selected as controls (≥60 years). The age, gender and anamnesis were matched in two groups of elderly people. The ELISA was used to detect the plasma levels of 8-iso-PGF2αin two groups of patients. And NIHSS score was used to evaluate the severity of clinical neurological deficit. Results The plasma levels of 8-iso-PGF2α were significantly higher in old ACI group (506.38±138.63) ng/L than those of middle-young ACI group (420.18±132.72) ng/L and old control group (369.98±99.81) ng/L. There was no significant difference in plasma level of 8-iso-PGF2αbetween middle-young ACI group and old control group (F=9.272,P<0.05). The NIHSS score was significantly higher in old group (19.78±3.66) than that of middle-young group (17.73 ± 2.70, t=2.539,P<0.05). There was a positive correlation between plasma 8-iso-PGF2α level and NIHSS score in old group (r=0.504,P=0.001). Conclusion The oxidative stress plays an important role in the occurrence and de-velopment process of ACI in elderly patients. The earlier and reasonable antioxidant therapy plays a positive role to alleviate the clinical symptoms and promote the recovery of illness.

Effects of bacterial lipopolysaccharide and normobaric hyperoxia on immature brain development of neonatal rat / 中华实用儿科临床杂志

Objective To investigate the effects of lipopolysaccharide (LPS) and / or normobaric hyperoxia on brain development of neonatal rat and the possible mechanisms.Methods One hundred and twenty postnatal day 2 (P2) SD rats were randomly assigned into 4 groups:air group,LPS group,hyperoxia group,LPS + hyperoxia group.General condition and body weight of the rats in each group were observed and recorded every day.The expression of active Caspase-3 and nuclear factor-κappaB P65 (NF-κB P65) in the brain were detected by immunohistochemistry staining on P7,and the level of IL-6 and 8-iso-PGF2α in the brain homogenate were measured by enzyme-linked immunosorbent assay(ELISA).The expression of myelin basic protein (MBP) in the brain was detected by immunohistochemistry staining on P12.Results The expressions of Caspase-3 and NF-κB P65 had the same trends:the number of positive cells from high to low was in LPS + hyperoxia group,LPS group/hyperoxia group,air group.There were significant differences between the first three groups and air group(all P ＜ 0.05).There were also significant differences between LPS + hyperoxia group and LPS group or hyperoxia group(all P ＜0.01).MBP in the brain had the completely reverse expression:from high to low order was in air group,hyperoxia group,LPS group,LPS + hyperoxia group.There were significant differences between the last three groups and air group (all P ＜ 0.05).There were also significant differences between LPS + hyperoxia group and LPS group or hyperoxia group(all P ＜0.01).The level of IL-6 in the brain from high to low order respectively was in LPS + hyperoxia group,LPS group,hyperoxia group,air group;and 8-iso-PGF2α was also in LPS + hyperoxia group,hyperoxia group,LPS group,air group,Significant differences were found among the four groups (all P ＜ 0.05).Conclusions Both postnatal infection and normobaric hyperoxia may induce premature rat brain injury,and increase the number of apoptosis cell and reduce the expression of MBP.The combination of infection and normobaric hyperoxia may aggravate the degree of brain damage of neonatal rat.NF-κB pathway mediated by Toll-like receptor may be involved in inflammation and oxidative stress,and may mediate Caspase-3 related apoptosis of nerve cell and white matter injury.

Patologías uterinas y fertilidad de vacas lecheras tratadas con dos inyecciones de PGF2α en las primeras 48 horas posparto / Uterine pathologies and fertility of dairy cows treated with two injections of PGF2α within the first 48 hours after calving

The objective of this work was to evaluate the effect of two injections of PGF2α within the first 48 hours after calving to decrease the incidence of uterine pathologies and improve reproductive performance in dairy cows. Four hundred and forty five Holstein cows with average milk yield of 10 100 kg per lactation were used. On calving day, cows were assigned in two groups, according to parity. Cows in the PGF2α group (n = 180) received a dose of 500 mcg of cloprostenol sodium by intramuscular injection within the first 12 h of calving and a second injection 48 h later; cows in the control group (n = 265) received nothing. All cows were examined via rectal palpation on day 7 postpartum; the type of pathology [placental retention (PR), haemorrhagic metritis (HM) and purulent metritis (PM)] was recorded. All cows were inseminated under the same reproductive program. Pregnancy diagnosis was carried out on day 45 after insemination by rectal palpation. The percentage of cows showing PR was lower (P < 0.05) in the PGF2α group (3%) than in the control group (10%); the percentage of cows with HM and PM was similar (P > 0.05) between groups [HM (PGF2α = 28.3% vs control = 31.6%) and PM (PGF2α = 43% vs control = 42.7%)]; the average interval from calving to first estrus was lower (P < 0.05) in cows of the PGF2α group (32.5 ± 1.7 days) than in the control group (42.1 ± 2.3 days); the average interval from calving to fist service was similar (P > 0.05) between groups (PGF2α = 76 ± 1.7 vs control = 80 ± 1.7days); the pregnancy rate on day 90 postpartum was greater (P < 0.05) in PGF2α group (38%) than in the control group (24.3%). It is concluded that PGF2α injection within the first 12 h postpartum and a second one 48 h after, decreases the incidence of placental retention, shortens the calving-first estrus interval and increases pregnancy rate on day 90 postpartum.

En el presente estudio se probó si la administración de dos inyecciones de PGF2α en las primeras 48 h posparto, disminuye la incidencia de patologías uterinas y favorece la fertilidad en vacas lecheras. Se utilizaron 445 vacas Holstein de diferente número de parto con una producción promedio de 10 100 kg de leche por lactancia. El día del parto las vacas se asignaron a dos grupos balanceando la proporción de vacas con diferente número de parto: grupo PGF2α (n = 180), estas vacas recibieron una inyección de 500 mcg de cloprostenol sódico, vía intramuscular, dentro de las primeras 12 h posparto, y una segunda inyección 48 h después. El grupo testigo (n = 265) no recibió PGF2α. Todas las vacas tuvieron una revisión vía rectal el día 7 posparto, se registró el tipo de padecimiento [retención placentaria (RP), metritis hemorrágica (MH) y metritis purulenta (MP)]. Todas las vacas fueron inseminadas bajo el mismo programa reproductivo. El diagnóstico de gestación se realizó el día 45 posinseminación mediante palpación rectal. El porcentaje de vacas que presentaron RP fue menor (P < 0.05) en el grupo PGF2α (3%) que en el grupo testigo (10%); la proporción de vacas que padecieron MH y MP fue similar (P > 0.05) entre los grupos [MH (PGF2α=28.3% vs testigo=31.6%) y MP (PGF2α=43% vs testigo=42.7%)]; la media del periodo del parto al primer estro fue menor (P < 0.05) en las vacas del grupo PGF2α (32.5 ± 1.7 días) que en el testigo (42.1 ± 2.3 días); la media del periodo del parto al primer servicio fue similar (P > 0.05) entre los grupos (PGF2α=76 ± 1.7 vs testigo=80 ± 1.7 días); el porcentaje de vacas gestantes al día 90 posparto fue mayor (P < 0.05) en el grupo PGF2α (38%) que en el testigo (24.3%). Se concluye que la inyección de PGF2α dentro de las primeras 12 h posparto, y una segunda inyección 48 h después, reduce la incidencia de retención placentaria, acorta el periodo del parto al primer estro y aumenta el porcentaje de vacas gestantes al día 90 posparto.