[Comparative study on the efficacy and safety between pegfilgrastim (PEG-rhG-CSF) and recombinant human granulocyte colony-stimulating factor in promoting hematopoietic recovery after allogeneic hematopoietic stem cell transplantation after hematological malignancy].

Objective: To observe the efficacy and safety between Pegfilgrastim (PEG-rhG-CSF) and Recombinant human granulocyte colony stimulating factor (rhG-CSF) in hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 157 patients after allo-HSCT were enrolled in this study from June 2015 to November 2016. Two agents of G-CSF were used to stimulate hematopoietic recovery after transplantation. There were 65 cases in PEG-rhG-CSF and 92 cases in rhG-CSF groups. Patients in PEG-rhG-CSF group were given a single subcutaneous dose of 6 mg on the first day and +8 d, while cases in rhG-CSF group were given in dose of 5 µg·kg(-1)·d(-1) by subcutaneous injection from +1 d continuing to neutrophils more than 1.5×10(9)/L, and then the indicators and survival rates in two groups after transplantation were compared. Results: ①There were no significant differences of the neutrophil implantation time[13.5 (8-12) d vs 13 (9-24) d, P=0.393] and platelet implantation time [14 (9-160) d vs 14 (9-92) d, P=0.094] between PEG-rhG-CSF and rhG-CSF groups respectively. There were no significant differences in terms of neutropenia period (P=0.435) , number of cases who got fever during neutropenia (P=0.622) , and the median time of fever in neutropenia period (P=0.460) , respectively between the two groups. There were no significant differences of erythrocyte and platelet transfusions (P=0.074, P=0.059) within 1 month after transplantation. ②There were no significant differences with regard to the incidences of acute GVHD[23.1% (15/65) vs 34.8% (32/92) , P=0.115], chronic GVHD[20.0% (13/65) vs 32.6% (32/92) , P=0.081], Ⅱ-Ⅳdegree of acute GVHD[30.0% (13/65) vs 30.4% (30/92) , P=0.287] and extensive chronic GVHD[9.2% (6/65) vs 20.7% (19/92) , P=0.135] between PEG-rhG-CSF and rhG-CSF groups. ③There were no significant differences in terms of disease free survival (DFS) (62.5% vs 61.4%, P=0.478) and overall survival (OS) (67.4% vs 67.3%, P=0.718) between PEG-rhG-CSF and rhG-CSF groups. ④There was no significant difference of the non-relapse mortality (NRM) between PEG-rhG-CSF and rhG-CSF groups[20.5% (95%CI 11.4%-37.0%) vs 32.6% (95%CI 22.2%-47.9%) , P=0.141]. The relapse rate was not statistically significant[14.9% (95%CI 7.4%-29.8%) vs 10.0% (95%CI 5.0%-20.0%) , P=0.299]. Conclusion: Compared with rhG-CSF, PEG-rhG-CSF could reduce the times of injection. There were no differences in terms of hematopoietic recovery, the incidence of GVHD, relapse rate, DFS and OS rates after allo-HSCT between two groups.

[Clinical efficacy of recombinant activated factor â ¦ a for 16 hematonosis with moderate or severe bleeding].

Objective: To analyze the efficacy of recombinant activated factor Ⅶ a (rF Ⅶ a) on hematonosis with moderate or severe bleeding signs. Methods: Of total 16 cases with rF Ⅶ a treatment from May 2013 to May 2016, 8 cases received allogeneic hematopoietic stem cells transplantation (allo-HSCT) and the other were non-transplantation patients. In two groups, there was no significant difference on rF Ⅶ a usage and dosage. 15 patients with acute graft-versus-host disease (aGVHD) after allo-HSCT were control group (without rF Ⅶ a) . Results: ①The total response rate was 75.0% (6/8) in non-transplantation group and 37.5% (3/8) in transplantation group, respectively. Median interval for hemorrhage stop was 38.5 hours in non-transplantation group and 63.0 hours in transplantation group. The median overall survival (OS) was 201.0 and 29.0 days for non-transplantation group and transplantation group, respectively, and the OS rate was 50.0% (4/8) and 25.0% (2/8) , respectively. The bleeding-related mortality rate was 50.0% (2/4) and 83.3% (5/6) , respectively. ②Of the 16 cases, 9 showed response to rF Ⅶ a treatment and the other 7 cases'bleeding signs did not alleviate. The median OS was 268.0 in 9 cases with response and 24.0 days in 7 cases without response, respectively. ③In patients with intestinal aGVHD complicated with intestinal hemorrhage, the median OS of observation group (n=6) and control group (n=15) were 25.5 days and 20.0 days, respectively. Conclusion: Patients with hematological diseases, especially patients after allo-HSCT, had high bleeding-related mortality, and rFⅦa therapy had a obvious hemostatic efficacy. The survival rate of patients with response was higher than that of cases without response. The causes of poor hemostasis efficacy of rF Ⅶ a therapy were associated with unsatisfactory control of complications in patients with intestinal bleeding after allo-HSCT.

A modified compression model of spinal cord injury in rats: functional assessment and the expression of nitric oxide synthases.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate a modified compression model of spinal cord injury (SCI) in adult rats by using a room-air- inflated Fogarty balloon catheter. SETTING: Kaohsiung, Taiwan. METHODS: The rats were divided into injury, sham-operated and control groups. A 2-French Fogarty catheter was passed from the lumbar spine (L3-L4) epidurally, with a mini-laminectomy under the microscope, to the level of thoracic spine (T6-T7). The actual site of the catheter tip was confirmed with X-ray. The balloon of Fogarty catheter then was inflated with room air, 0.2 ml, for 10 min. Mini-laminectomy was performed without inserting the catheter in the sham-operated group. Quantitative neurological outcomes were evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale daily. The gene expression of nitric oxide synthases (NOSs) of the spinal cord was investigated at the end of the functional assessment. RESULTS: The mean BBB locomotor scores were 10±1.85 and 10±1.85, respectively, on days 1 and 3 in the injury group, and 21 and 20.29±0.69, respectively, in the sham-operated group. There was a significantly increased gene expression of inducible NOS in the SCI group compared with the sham-operated group and control group. Endothelial NOS gene expression was not significantly different among the groups. CONCLUSION: The functional and molecular assessments show that this modified balloon-compression technique is a reproducible, simple and inexpensive model of SCI in rats.

Posterior sclera reinforcement and phakic intraocular lens implantation for highly myopic amblyopia in children: a 3-year follow-up.

PURPOSE: To study the safety and efficacy of posterior scleral reinforcement (PSR) combined with phakic intraocular lens (PIOLs) implantation for highly myopic amblyopia in children. METHODS: This study included eight highly myopic children (11 eyes) who failed in conventional therapy for amblyopia using various combination of spectacles, contact lenses, and intensive patching before enrollment into this study. They were treated sequentially with PSR and PIOL implantation, and were followed up for 3 years after surgery. Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) in LogMAR, spherical equivalent power (SE), and complications were evaluated. RESULTS: Before surgery, the mean UCVA was 1.59±0.33, BCVA, 0.74±0.37, SE, -17.57±5.56D, the axial length (AL), 30.09±2.18 mm. After PSR, BCVA improved one line in three patients, the rest were unchanged, and AL was unchanged among all cases. Six eyes of three patients were implanted with an iris-claw PIOL and five eyes of five patients were implanted with a posterior PIOL. After completion of treatment, the mean UCVA was 0.44±0.21, BCVA 0.38±0.24, SE -0.54±0.74 D, and AL 30.35±2.29 mm. No patient experienced complications. CONCLUSION: Combined PSR and PIOL implantation treatment for highly myopic amblyopia in children is safe and effective.

Dosimetric and efficiency comparison of high-dose radiotherapy for esophageal cancer: volumetric modulated arc therapy versus fixed-field intensity-modulated radiotherapy.

The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted.

Comparison of anastomotic leakage and stricture formation following layered and stapler oesophagogastric anastomosis for cancer: a prospective randomized controlled trial.

The objective of this prospective, randomized, controlled trial, conducted from May 2002 to December 2007, was to compare post-operative anastomotic leakage and stricture formation following layered manual versus stapler oesophagogastric anastomosis in patients who underwent resection of oesophageal or gastric cardia carcinoma. Patients (n = 516) were randomized to receive either layered manual or circular stapled oesophagogastric anastomosis. Mean follow-up time was > 12 months. Anastomotic leakage occurred in one (0.4%) patient in the layered group and six (2.2%) in the stapler group; no statistically significant between-group difference. After operation, two (0.8%) patients in the layered group and 13 (5.0%) in the stapler group developed a benign oesophageal stricture; the difference between the groups was statistically significant. Compared with stapler anastomosis, layered manual anastomosis may significantly reduce the incidence of anastomotic strictures. This method is easy to apply and could be used as an alternative procedure for oesophagogastric anastomosis after resection for oesophageal or cardia carcinoma.

Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

Evaluation of sampling tools for environmental sampling of bacterial endospores from porous and nonporous surfaces.

AIMS: Having and executing a well-defined and validated sampling protocol is critical following a purposeful release of a biological agent for response and recovery activities, for clinical and epidemiological analysis and for forensic purposes. The objective of this study was to address the need for validated sampling and analysis methods called out by the General Accounting Office and others to systematically compare the collection efficiency of various swabs and wipes for collection of bacterial endospores from five different surfaces, both porous and nonporous. This study was also designed to test the collection and extraction solutions used for endospore recovery from swabs and wipes. METHODS AND RESULTS: Eight collection tools, five swabs and three wipes, were used. Three collection/preservation solutions were evaluated: an ink jet aerosol generator was used to apply Bacillus subtilis endospores to five porous and nonporous surfaces. The collection efficiencies of the swabs and wipes were compared using a statistical multiple comparison analysis. CONCLUSIONS: The ScottPure wipe had the highest collection efficiency and phosphate-buffered saline (PBST) with 0.3% Tween was the best collection solution of those tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Validated sampling for potential biological warfare is of significant importance and this study answered some relevant questions.

The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm.

BACKGROUND: Adenosine is a potent vasodilator and an important modulator of cardiovascular function. It has been postulated that nitric oxide (NO) is involved in adenosine-induced vasodilation. This study was designed to examine the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the prevention of subarachnoid haemorrhage (SAH)-induced vasospasm. Method. Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 mL autogenous blood into the cisterna magna. Intraperitoneal injections of CPA (0.003 mg/kg), or vehicle were administered 5 min and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging the cross sectional areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar artery were evaluated. Findings. There were no significant differences among the control and treated groups in physiological parameters recorded before sacrifice. When compared with animals in the control group, cross-sectional area of basilar arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The cross-sectional areas of the CPA-treated group differed significantly from those of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and protein in basilar artery by SAH was not significantly diminished by CPA. The SAH-induced suppression of eNOS-mRNA and protein were relieved by CPA treatment. Conclusions. This is the first evidence to show an adenosine A1 receptor agonist is effective in partially preventing SAH-induced vasospasm without significant cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in attenuating SAH-induced vasospasm may be, in part, related to preserve the normal eNOS expression after SAH. Inability in reversing the increased iNOS expression after SAH may lead to the incomplete anti-spastic effect of CPA.

Induction of vascular endothelial growth factor expression in human pulp fibroblasts stimulated with black-pigmented Bacteroides.

AIM: To investigate the effect of black-pigmented Bacteroides on the expression of vascular endothelial growth factor (VEGF) gene in human pulp fibroblasts. METHODOLOGY: The supernatants of Porphyromonas endodontalis, Porphyromonas gingivalis and Prevotella intermedia were used to evaluate VEGF gene expression in human pulp fibroblasts. The levels of mRNAs were measured by the quantitative reverse-transcriptase polymerase chain reaction analysis. RESULTS: Black-pigmented Bacteroides induced significantly high levels of VEGF mRNA gene expression in human pulp fibroblasts (P < 0.05). In addition, the expression of VEGF depended on the bacteria tested. CONCLUSIONS: Black-pigmented Bacteroides may be involved in developing pulpal disease through the stimulation of VEGF production that would lead to the expansion of the vascular network coincident to progression of the inflammation.

Spinal chronic subdural hematoma in a patient with ventriculo-peritoneal shunting after a minor trauma.

STUDY DESIGN: Case report and review of literature. OBJECTIVES: Intracranial chronic subdural hematoma (SDH) is a well-recognized complication of ventriculoperitoneal (VP) shunt. Spinal chronic SDH is very rarely associated with VP shunt. SETTING: Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. CASE REPORT: We describe a spinal chronic SDH, developing after a minor trauma, in a patient who underwent a VP shunt surgery for hydrocephalus 6 months previously. A good outcome was achieved after decompressive surgery. CONCLUSION: Spinal chronic SDH should be considered in the diagnosis of progressive spinal compression, especially in the patients with VP shunt after minor trauma.

A new phenolic glycoside and a new trans-clerodane diterpene from Conyza blinii.

A new phenolic glycoside, 4-propionyl-2,6-dimethoxyphenyl beta-D-glucopyranoside (1) and a new trans-clerodane diterpene named 19-deacetylconyzalactone (2), were isolated from the aerial parts of Conyza blinii.

Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception.

Evidence suggests both opioid mu and delta receptors may participate in the regulation of respiration at different central nervous system sites. In the past, the overlapping receptor specificity of various opioid drugs has made it difficult to dissect the receptor subtype-specific activities involved in respiratory regulation. The new family of delta receptor selective agents such as cyclic[D-Pen2, 5]enkephalin, deltorphins, (+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide, naltrindole and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH have now made it feasible to more clearly define the role of delta receptors in respiratory control. In a series of experiments we observed that systemic infusion of rats with the highly mu receptor-specific opioid alfentanil induced antinociception and hypercapnia, and both of these effects were antagonized by the mu antagonist D-Phe-Cys-Tyr-Orn-Thr-Pen-Thr-NH2. However, peripheral administration of the delta receptor antagonist naltrindole reverses the hypercapnia but not the antinociceptive activity of alfentanil. This differential effect of naltrindole on antinociception and hypercapnia could also be produced with the delta agonist (+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide. In addition, intracerebroventricular delivery of a number of peptide delta ligands cyclic[D-Pen2,5]enkephalin, deltorpnin II and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH also produced the same differential reversal of hypercapnia without affecting antinociception. Thus, both the traditional delta agonists and antagonists are able to reverse the alfentanil-induced hypercapnia without affecting antinociception. The reversal of alfentanil-induced hypercapnia by these delta ligands was antagonized by a novel synthetic delta antagonist cis-4-(alpha-(4-((Z)-2-butenyl)-3, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide. We propose that in this experimental respiration model, the delta antagonists naltrindole and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH behave like delta agonists with low but sufficient intrinsic activities to reverse alfentanil-induced hypercapnia in rats. The results suggest that a function of the delta receptor is to modulate or counteract the respiratory depression induced by the mu receptor.

Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control.

BACKGROUND AND OBJECTIVES: Ketamine is currently the only N-methyl-D-aspartate receptor channel blocker in clinical use. This study evaluated the analgesic efficacy of epidurally coadministered ketamine and morphine in postoperative pain control. METHODS: The patient population consisted of ASA class I and II patients undergoing major joint replacement. Epidural lidocaine was used as the primary anesthesia for the surgery. In phase I of the study, either ketamine (10-30 mg) or morphine (0.5-2 mg) was administered via epidural catheter immediately after surgery. This was done to evaluate the dose-response effect of these drugs when used for postoperative pain relief, and the results were applied to phase II of the study, in which all patients received ketamine pretreatment (total 30 mg) with each dose of lidocaine administered before and during surgery. Forty patients were randomly divided into four groups, each of which received one of three different pain control regimens mixed with 10 ml of saline: group B received 10 mg ketamine, group C 2 mg morphine, and group D 10 mg ketamine plus 0.5 mg morphine while the control group A received 10 mL of saline with no additive. The intensity of pain expressed by patients, as well as the number of intramuscular meperidine (1 mg/kg) injections administered and any side effects that may have occurred, were recorded. RESULTS: Ketamine produced no significant pain relief. A 2-mg morphine dose did produce significant analgesia but was accompanied by a high incidence of side effects. Co-administration of subanalgesic doses of ketamine, 10 mg and morphine, 0.5 mg, however, also produced a strong analgesic effect. CONCLUSIONS: Ketamine, although not itself an epidural analgesic agent, potentiates the analgesic effect of morphine, especially when administered as a pretreatment. The resulting lowered dosage of epidural morphine needed for postoperative pain relief reduces, in turn, the incidence of side effects. Pretreatment of patients with ketamine epidurally, followed by injections of combined morphine and ketamine could be a promising new analgesic regimen.

Opioid agonist binding affinity is increased by magnesium in the presence of guanosine diphosphate but decreased by magnesium in the presence of guanyl-5'-yl imidodiphosphate.

Opioid receptors exist in multiple affinity states for agonists. Cations and guanine nucleotides affect mu-agonist affinity by modulating the interaction between receptor molecule and G-protein. In this study, we systematically examined the effects of cations and guanine nucleotides on the binding of mu-agonist [D-Ala2, N-Me-Phe4, Met-(O)5-ol]enkephalin in rat spinal cord and brain membranes. A homogeneous class of low-affinity receptors was obtained by conducting binding assays in the presence of Na+ (100 mM) + guanosine diphosphate (100 microM). The addition of Mg++ (5 mM) shifted a portion of the low-affinity receptors to the high-affinity state. In membranes preincubated with Na+ + guanosine diphosphate and with the binding assay performed in the presence of Mg++, a homogeneous class of high-affinity receptors was induced by the agonist. Further addition of Na+ + guanyl-5'-yl imidodiphosphate (30 microM) to the above Mg++-containing medium converted all receptors to a low-affinity state, whereas Na+ + guanyl-5'-yl imidodiphosphate produced a mixture of high- and low-affinity states. Our results suggest that, depending on which guanine nucleotide is bound with G-proteins, mg++induces opposite effects on the states of mu-receptor affinity: high affinity with GDP and low affinity with guanyl-5'-yl imidodiphosphate. Sodium ion promotes the low-affinity receptor conformation and increases total low-affinity binding sites. The affinity of the opiod antagonist naloxone is not sensitive to regulation by Mg++ and guanine nucleotides, except that the total receptor binding is increased by Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Bactericidal antibiotics increase tumor necrosis factor-alpha and cardiac output in rats after cecal ligation and puncture.

We hypothesized that treatment of experimental sepsis with bactericidal antibiotics, known to enhance microbial toxin release, would alter tumor necrosis factor-alpha production and the hemodynamic response to the syndrome. In the rat, after cecal ligation and puncture (CLP), elevated serum TNF levels and cardiac output were observed following antibiotic treatment. TNF and cardiac output were elevated to a greater extent in bactericidal-treated than bacteriostatic-treated or antibiotic-untreated rats. Animals treated with bactericidal antibiotics also had significantly greater cardiac outputs than untreated rats. Despite increases in circulating TNF with antibiotic administration, the mortality rate at 96 hr decreased after either bactericidal or bacteriostatic antibiotics. We conclude that elevated TNF after CLP in rats treated with antibiotics is associated with enhanced hemodynamic responses to CLP, but does not increase early mortality. In this model of polymicrobial sepsis, bactericidal and bacteriostatic antibiotics led to different hemodynamic effects without compromising survival.

Protection against platelet-activating factor-induced injury by interferon inducer in perfused rabbit lung.

Platelet-activating factor (PAF) and the interferons (IFN) are released during sepsis and the adult respiratory distress syndrome. The proinflammatory nature of PAF and anti-inflammatory property of IFN led us to investigate interactions between these two mediators in an isolated perfused lung (IPL) preparation. In the IPL, mean pulmonary arterial pressure (Ppa), lung weight gain, and peak airway pressure (Paw) were monitored continuously for 1 h in six groups of rabbits: 1) control, 2) the IFN-alpha/beta inducer polyinosinic:cytidylic acid (polyI:C) alone, 3) PAF alone, 4) polyI:C + PAF, 5) indomethacin + PAF, and 6) AA861 (a 5-lipoxygenase inhibitor) + PAF. At the end of 1 h, microvascular pressure was determined by double-occlusion technique and partition of total pulmonary vascular resistance (RT) was calculated. Serial eicosanoid concentrations in the perfusate also were measured. PAF increased Ppa, Paw, lung weight gain, and RT. These changes were associated with increased thromboxane B2 and decreased leukotriene production. PolyI:C, which induced high levels of serum IFN in rabbits, blocked the PAF-induced increase in Ppa, Paw, lung weight gain, and RT, similar to indomethacin and AA861. PolyI:C suppressed PAF-stimulated release of thromboxane B2 and increased leukotriene levels in the perfusate. The PAF-induced lung responses also were attenuated by pretreatment with human recombinant IFN. These data indicate that polyI:C protects against PAF-induced responses in the rabbit IPL, most likely via its induction of IFN. This effect is related in part to inhibition of thromboxane A2 production stimulated by PAF and leukotrienes.

Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain.

Monoamine oxidase (MAO) as a source of hydrogen peroxide (H2O2) was evaluated during ischemia-reperfusion in vivo in the rat brain. H2O2 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H2O2 by catalase during ischemia and reperfusion was measured in forebrain homogenates using aminotriazole (ATZ), an irreversible H2O2-dependent inhibitor of catalase. Catecholamine and glutathione concentrations in forebrain were measured with and without MAO inhibitors. During ischemia, forebrain blood flow was reduced to 8% of baseline and H2O2 production decreased as measured at the microperoxisome. During reperfusion, a rapid increase in H2O2 generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The H2O2-dependent rates of ATZ inactivation of catalase between control and ischemia-reperfusion were similar, indicating that H2O2 was more available to glutathione peroxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H2O2 production and increased the catecholamine concentrations. Mortality was 67% at 48 h after ischemia-reperfusion, and there was no improvement in survival after inhibition of MAO. We conclude that MAO is an important source of H2O2 generation early in brain reperfusion, but inhibition of the enzyme does not improve survival in this model despite ablating H2O2 production.