In order to find out the relationship between arachidonic acid(AA) metabolites and the development of vasospasm following a subarachnoid hemorrhage(SAH), we evaluated the cerebrospinal fluid(CSF) levels of the two main AA metabolites, prostacyclin(PGI2) and thromboxane A2(TXAZ) by measuring their stable degredation products 6-keto-prostaglandin F1alpha(PGF1) and thromboxane B2(TXB2) using radioimmunoassay methods in 32 patients after an aneurysmal rupture and in 11 patients without an aneurysmal rupture as a control group. We compared the data between aneurysmal ruptured patients and control group patients. We also divided the data of the aneurysmal ruptured patients into 3 groups checking them between 1-4, 5-11, and 12-28 days after the SAH, and compared the data among the groups, then the data was also compared between non-vasospasm and clinical or severe angiographic vasospasm groups of patients. The results showed that the AA metabolism was enhanced after the SAH, The TXB2 increased the greatest amount in 1-4 days after the SAH and significantly decreased statistically 12 days after the SAH(p<0.002). This study also showed that the TXB2 level was significantly higher statistically in 1 to 4 days in the clinical or angiogrophically severe vasospasm group than in the non-vasospasm group of patients(p<0.032). PGF1 did not show any statistically significant changes according to the number of SAH days or a difference between the vasospasm and non-vasospasm groups. This result suggests if the AA metabolites are involved in the pathogenesis of cerebral vasospasm, and the lumbar CSF levels of AA metabolites in aneurysmal patients reflect the arterial synthesis of PGI2 and platelet origin of TXA2, the elevation of TXA2 or other vasoconstrictor prostaglandins is more likely to play a major role in the pathogenesis of vasospasm than PGI2 deficiency. The measurements of the CSF TXB2 in 1 to 4 days after a SAH may have an expectant value in the development of clinical or severe angiographic vasospasm(exclude the accompanying intraventricular hemorrhage patients).
Aneurysm* ; Arachidonic Acid ; Blood Platelets ; Cerebrospinal Fluid* ; Epoprostenol ; Hemorrhage ; Humans ; Metabolism ; Prostaglandins I ; Radioimmunoassay ; Rupture ; Subarachnoid Hemorrhage* ; Thromboxane A2 ; Thromboxane B2* ; Vasospasm, Intracranial

BACKGROUND AND OBJECTIVES: Prostaglandin is one of the important inflammatory mediator in inflammatory diseases. Cyclooxygenase-2 (COX-2) plays a key role in biosynthesis of prostaglandins. In this study, we aimed to investigate COX-2 expression and prostaglandin E2 (PGE2) production by interleukin-1beta (IL-1beta) in cultured human airway epithelial cells. MATERIALS AND METHOD: COX-2 gene expression, and COX-2 protein, PGE2 production by IL-1beta were analyzed by RT-PCR, Western blot, and enzymeimmunoassay (EIA) in cultured human airway NCI-H292 epithelial cells. RESULTS: The COX-2 protein production was increased when the cells were exposed to IL-1beta in a dose dependent manner. The maximum level of COX-2 protein was detected at 20 ng/ml of IL-1beta. After 4 hours, the production of COX-2 protein was detected by IL-1beta(20 ng/ml) and this was held up to 12 hour. The maximum level of COX-2 protein production reached at 8 hour of exposure to IL-1beta and this was held up to 12 hour. The release of PGE2 occurred in the same pattern as the IL-1beta-mediated COX-2 protein production. The COX-2 gene expression was induced by IL-1beta (20 ng/ml). The IL-1beta-mediated COX-2 expression was suppressed by actinomycin D, but was not affected by cycloheximide. CONCLUSION: These results suggest that the IL-1beta-mediated COX-2 expression and the PGE2 production were increased in dose and time dependent manner and regulated in the transcriptional step.
Blotting, Western ; Cycloheximide ; Cyclooxygenase 2 ; Dactinomycin ; Dinoprostone ; Epithelial Cells* ; Gene Expression ; Humans* ; Interleukin-1beta ; Prostaglandins ; Prostaglandins I

An increase in the number of preterm infants and a decrease in the gestational age at birth have resulted in an increase in the number of patients with significant bronchopulmonary dysplasia (BPD) and secondary pulmonary hypertension (PH). PH contributes significantly to the high morbidity and mortality in the BPD patients. Therefore, regular monitoring for PH by using echocardiography and B-type natriuretic peptide (BNP) or N-terminal-proBNP must be conducted in the BPD patients with greater than moderate degree to prevent PH and to ensure early treatment if PH is present. In the BPD patients with significant PH, multi-modality treatment, including treatment for correcting an underlying disease, oxygen supply, use of diverse selective pulmonary vasodilators (inhaled nitric oxide, inhaled prostacyclins, sildenafil, and endothelin-receptor antagonist) and other methods, is mandatory.
Bronchopulmonary Dysplasia ; Dietary Sucrose ; Echocardiography ; Epoprostenol ; Gestational Age ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary ; Infant ; Infant, Newborn ; Infant, Premature ; Natriuretic Peptide, Brain ; Nitric Oxide ; Oxygen ; Parturition ; Piperazines ; Prostaglandins I ; Purines ; Sulfones ; Vasodilator Agents ; Sildenafil Citrate

PURPOSE: Prostaglandins(PGs) are known to produce a remarkably broad spectrum of effects that embraces practically every biological function, and has a particular physiological role in the central nervous system. Significant increases of PGs levels are seen in certain diseases, such as febrile infection, stroke, schizophrenia, and epilepsy. Prostaglandin is also increased in a response to rising body temperature, and prostaglandin E-2(PGE-2) in lumber cerebrospinal fluid is also increased in febrile convulsion. Intracerebroventricular injection of PGE produces a rise in body temperature and also antagonizes convulsions induced by pentylenetetrazole, penicillin, electric shock. Therefore we studied PGE-2 levels in cerebrospinal fluid of afebrile children, children with febrile convulsion, and febrile children without convulsion. METHODS: The subjects comprised 57 cases with febrile convulsion, 24 cases of afebrile diseases and 9 febrile children without convulsion. All patients were undergoing lumbar puncture and PGE-2 levels in CSF were determined by highly specific radio-immunoassay(Prostaglandin E2 [125I] assay system, Biotra Assays, Amersham Inc.). RESULTS: 1) The CSF PGE-2 levels were significantly higher in children with febrile convulsion(147.3+/-79.3pg/ml) than those in febrile children without convulsion(72.4+/-75.4pg/ml) and afebrile children(19.2+/-28.4pg/ml)(p<0.05). 2) There were no statistical significances of the CSF PGE-2 levels between age and fever in both groups. 3) The CSF PGE-2 levels within 4 hours(176.5+/-65.7pg/m1) after convulsions were significantly higher than those 4 hours after convulsion(93.3+/-74.9pg/ml). CONCLUSION: The CSF PGE-2 levels were significantly higher in children with febrile convulsion than those in febrile children without convulsion and those in afebrile child ran. The CSF PGE-2 levels within 4 hours after convulsion were significantly higher than those 4 hours after convulsion.
Body Temperature ; Central Nervous System ; Cerebrospinal Fluid* ; Child* ; Epilepsy ; Fever ; Humans ; Penicillins ; Pentylenetetrazole ; Prostaglandins E ; Prostaglandins I ; Schizophrenia ; Seizures ; Seizures, Febrile* ; Shock ; Spinal Puncture ; Stroke

BACKGROUND: Prostaglandin system is known to participate in manifestation of the renin-angiotensin system. However, role of prostaglandins on the renin-angiotensin system in development of hypertension is not well established. This study was to examine whether the role of prostaglandins is altered in experimental hypertension. METHODS: Two-kidney, one-clip(2KIC) renal hypertension was made by clipping the left renal artery with a silver clip(internal gap of 0.2mm) and deoxycorticosterone acetate (DOCA)-salt hypertension by subcutaneous implantation of DOCA(200mg/kg) strip plus saline(1%) drinking. They were used 3 weeks later. Age-matched normal rats served as a control. Femoral artery was cannulated and arterial blood pressure and heart rate were monitored continuously. RESULTS: 1) In normotensive rats, saralasin infusion(20 microg/kg/min, IV) caused a decrease in mean arterial pressure without significant alterations in heart rate. Indomethacin-pretreatment(10mg/kg, IP) abolished the depressor response to saralasin. 2) The depressor response to saralasin was more marked in renal hypertensive rats than in normotensive rats. The magnitude of maximum decrease in blood pressure, however, was comparable between the hypertensive and normotensive rats. Indomethacin-pretreatment did not affect the depressor response to saralasin in renal hypertensive rats. 3) In DOCA-salt hypertensive rats, saralasin infusion rather caused an increase in mean arterial pressure without significant alterations in heart rate. The pressor response to saralasin was not affected by indomethacin-pretreatment. CONCLUSION: These results indicate that prostaglandin system may modify renin-angiotensin system in normotensive rats. It is suggested that mechanisms other than prostaglandin system participate in the full-blown manifestation of renin-angiotensin system in 2KIC renal hypertensive rats.
Animals ; Arterial Pressure ; Blood Pressure ; Desoxycorticosterone ; Drinking ; Femoral Artery ; Heart Rate ; Hypertension ; Hypertension, Renal ; Prostaglandins I ; Prostaglandins* ; Rats* ; Renal Artery ; Renin-Angiotensin System* ; Saralasin ; Silver

Ureteral obstruction causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Although increased renal prostaglandin production is responsible for the former, it is not clear whether or not it is also responsible for the latter. Therefore, we investigated the role which prostaglandins play in the autoregulation of RBF during an ureteral pressure elevation (40 cmH2O). Since the major mechanism of RBF autoregulation is the tubuloglomerular feedback studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. To pursue the purpose, six anesthetized dogs were prepared for the measurements of RBF, mean systemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from 170 +/- 8 ml cntdot min -1 to 189+/-8, and the systemic arterial pressure didn't change significantly. During spontaneous urine flow, RBF autoregulation was abolished when RAP was reduced to 59+/-3 mmHg. On the other hand, during the ureteral pressure elevation, the autoregulation curves shifted upward and rightward from control, and the pressure when RBF autoregulation was abolished was 74 +/- 3 mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulation during both control (63 +/- 5 mmHg) and the elevated ureteral pressure (77 +/- 5 mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatory capacity during partial ureteral obstruction. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at spontaneous RAP and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.
Animals ; Arterial Pressure ; Dogs* ; Hand ; Homeostasis ; Indomethacin ; Kidney ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; Prostaglandins I ; Renal Circulation* ; Social Control, Formal* ; Ureter* ; Ureteral Obstruction* ; Urinary Catheters ; Vasodilation

Apoptosis is a physiologic or programmed cell death process which is controlled by genes and it is essential for the function and the appropriate development of multicellular organism. Apoptosis is also thought to be one of the main mechanisms of cell death in ischemic tissues. The effect of prostaglandin E1(PGE1) is proven to be useful in the recovery of ischemic changes by inducing vasodilation of peripheral vessels and platelet disaggregation. Prostaglandin is also known to suppress apoptosis in a serum deprived cell. The purpose of this study is to evaluate the effects of PGE1 on the apoptosis in the ischemic skin island flap. Thirty Sprague-Dawley rats were used. In control group(n=15), 3x5cm sized skin island flap based on the superficial epigastric vessel was elevated and its pedicle was occluded for 14 hours. After removing the vessel clamp, skin flap was reperfused for 5 hours and harvested. In experimental group(n=15), a ischemic skin island flap was also made as in the control group except the interarterial administration of the PGE1 right after elevation of the flap and after removing the clamp. H&E, TUNEL and immunohistochemical stains for p53 and bax proteins were performed. There were ischemic changes in gross and microscopic findings in both groups. Immunohistochemical staining for p53 protein shows many positive cells with nuclear staining in squamous epithelium of the control group, but sparse positive cells in the experimental group. Immunohistochemical stainings for bax protein shows many positive cells with cytoplasmic staining in squamous epithelium of the control group, but sparse positive cells in the experimental group. The apoptotic index was significantly lower in the experimental group(2.39+/-1.76(p=0.0001)) than in the control group(7.53+/-2.05). These data indicate that PGE1 suppresses the apoptosis in the ischemic skin island flap.
Alprostadil* ; Animals ; Apoptosis ; bcl-2-Associated X Protein ; Blood Platelets ; Cell Death ; Coloring Agents ; Cytoplasm ; Epithelium ; In Situ Nick-End Labeling ; Prostaglandins I ; Rats* ; Rats, Sprague-Dawley ; Skin* ; Vasodilation

OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.

METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).

RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).

CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

Interferon-gamma has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. Interferon-gamma slightly decreased [3H]thymidine incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-gamma whether it was determined by the [3H]proline incorporation rate or by the Lowry smethod. The effect of interferon-gamma on the individual protein was, however, differential, ie, it increased [3H]proline incorporation into the noncollagenous protein marginally, while it decreased [3H]proline incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of interferon-gamma. The differential effects of the interferon-gamma on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. Interferon-gamma decreased steady state level of alpha1(I) procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the interferon-gamma induced collagen decrease in this cell, which meant prostaglandins were not involved in the process of interferon-gamma induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of interferon-gamma for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.
Alkaline Phosphatase ; Bone Remodeling ; Collagen Type I ; Collagen* ; Connective Tissue ; DNA ; Enzyme-Linked Immunosorbent Assay ; Fibronectins* ; Gene Expression ; Indomethacin ; Interferon-gamma* ; Osteoblasts ; Periodontal Ligament* ; Procollagen ; Prostaglandins ; RNA, Messenger

Postpartum hemorrhage is a serious condition related with maternal morbidity and mortality. Prior to surgical treatment, oxytocin and prostaglandin analogs administration are common. Pyrexia after prostaglandin E1 was well known, but PG E2 has been shown to have a few complication even though coronary arterial spasm was rarely reported. The 38-year old woman who delivered 3rd baby by Cesarean section was developed the atonic uterine bleeding. During the treatment with high dose sulprostone (PG E2), she complained the anterior chest pain, her body temperature was elevated to 41.2 degrees C, and then convulsion with stuporous mentality was developed. EKG revealed inverted T wave in II. III, aVF lead, and CK-MB, troponin I was elevated. The laboratory test revealed elevated SGOT/SGPT, myoglobin, and metabolic acidosis. But CSF study, blood culture, direct/indirect Coomb's test, brain CT, and echocardiography were all negative. After supportive care, she came to be alert after 10 hours, body temperature was returned to normal after 22 hours, and the laboratory tests were eventually returned to normal within 6 days. She was discharged from the hospital without any complication. We postulate that high dose PG E2 resulted in high fever, coronary artery spasm, and convulsion
Acidosis ; Alprostadil ; Body Temperature ; Brain ; Cesarean Section ; Chest Pain ; Coombs Test ; Coronary Vessels ; Dinoprostone ; Echocardiography ; Electrocardiography ; Female ; Fever ; Humans ; Myoglobin ; Oxytocin ; Porphyrins ; Postpartum Hemorrhage ; Pregnancy ; Prostaglandins, Synthetic ; Seizures ; Spasm ; Stupor ; Troponin I ; Uterine Hemorrhage