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Biocrust communities provide a pallet of ecosystem services, such as soil stabilization, altering of hydrological cycles and primary production, and often are the first colonizers of unvegetated surfaces during succession. Therefore, artificially establishing biocrusts can improve soil properties, for example, by stabilizing bare soil surfaces against erosion or by accumulating nutrients. In this study, the establishment of artificial biocrusts was tested for the restoration of potash tailings piles that result from potash fertilizer production and mostly consist of NaCl. A biocrust cover as primary vegetation could decrease the saline seepage waters by trapping rainwaters, thereby reducing the environmental pollution. In a laboratory experiment, we created a salt gradient by mixing the tailings materials with non-saline dune sand. Surface material of the abandoned potash tailings pile Neuhof-Ellers (NE) and material of the Infiltration Hampering Stratum (IHS) were tested, along with a treatment with bone charplus (BCplus) and sodium alginate. A mixture of 50% (w/w) IHS and dune sand was most successful for the establishment of green biocrust microalgae, based on increased biomass and photosynthetic performance. The chlorophyll a content was negatively correlated with the electrical conductivity (EC), and was significantly increased in the BCplus and sodium alginate treatment, while biocrusts failed to establish on pure tailings piles substrates. The limit of the substrates EC for biocrust establishment was 35 mS cm−1. This limit provides a baseline for future studies that should use BCplus and sodium alginate to increase the success of biocrust establishment on potash tailings piles. [ABSTRACT FROM AUTHOR]

A new proton conducting material with a possible application as a membrane in fuel cells is synthesized. It is formed by nanocrystalline cellulose (NCC) doped with a different concentration of the imidazole molecules (Im) used as 'dry' conducting species. The nanocomposites (NCC-Im) are obtained in the form of films. Their chemical composition, thermal properties, and the electric conductivity are determined by elementary and thermogravimetric analysis, differential scanning calorimetry and impedance spectroscopy methods, respectively. The nanocomposite (1.7NCC-Im) with the highest concentration of imidazole i.e. one Im per 1.7 glucose unit shows the highest electrical conductivity equal to 2.7 × 10 S/m at 140 °C. This value is about five orders of magnitude higher than that of the pure NCC film at this same temperature. The important feature is that it is obtained for nanocomposite under anhydrous conditions. [ABSTRACT FROM AUTHOR]

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Purpose Uptake of cardiac rehabilitation services by older people is suboptimal. Offering suitable services may increase participation. This study investigated older heart failure patients' preferences between hospital, community and home-based service models and sociodemographic and clinical factors associated with these preferences. Rates of referral were examined. Methods Cross-sectional survey of patients aged 65 years and older consecutively admitted to elderly care, cardiology and general medicine wards in a large UK hospital with confirmed heart failure between March-December 2009. A 57-item interview schedule incorporating open and closed questions and standard measures was developed enabling both quantitative and qualitative analysis. Associations between patients' preferences and characteristics including disease severity (New York Heart Association [NYHA] classification) and comorbidity (Charlson comorbidity score) were analysed using Chi-squared tests and one-way ANOVA. Results One hundred and six interviews were completed (mean age 77.8±7.3, 62% male, 47% lived alone). Most patients had moderate-severe heart failure (55% NYHA class III; 34% class II) and co-morbidities (mean Charlson score 3.3±1.7). Most opted for cardiac rehabilitation (72%), preferring hospital to community classes. Those preferring hospital programmes were younger (mean 5.1 years, 95% CI -10.1 to -0.1, P=0.043) than those preferring not to participate. Neither disease severity nor comorbidity was associated with preferences. Only 21% were referred to any cardiac rehabilitation service. Conclusion Most of these older heart failure patients wanted to attend cardiac rehabilitation, but few were referred. Age was related to preferring certain cardiac rehabilitation service models but not to an overall preference to attend. Referral processes need urgent improvement and offering choice of service models may increase participation. [ABSTRACT FROM AUTHOR]

Background: Hernia repair in single-incision laparoscopic surgery (SIL) technique has become increasingly common at specialized centers. Still, safety issues and potential benefits of SIL hernia repair have to be elucidated. This review summarizes available literature and provides an overview of current developments. Materials and methods: A literature search was performed in PubMed, the Cochrane Database, and Google for peer-reviewed publications on SIL hernia repair. Main outcome parameters were defined, and it was attempted to define clinical recommendations. Results: SIL technique can be applied for inguinal, ventral, and hiatal hernia repair. Operation times and early results seem to be comparable with standard multiport laparoscopy. Conclusion: Distinct advantages of SIL hernia surgery have yet to be demonstrated, as the level of evidence in this field is low. Randomized controlled trials investigating the incidence of incisional hernias at the trocar site and safety in large cohorts are missing. [ABSTRACT FROM AUTHOR]

Background: Mesh reinforcement has become the standard of care in the open and laparoscopic repair of inguinal hernia. Chronic pain after inguinal hernia repair is often due to nerve injury by penetrating mesh fixation devices such as staples (ST), tacks, or sutures. In several studies on hernioplasty, atraumatic mesh fixation with fibrin sealant (FS) proved to be efficient in terms of fixation strength and elasticity. Unfortunately, most of these studies did not provide a standardized follow-up and assessment of the development of chronic pain (CP) and the quality of life (QoL). Therefore, a randomized controlled trial comparing CP and QoL after FS fixation of mesh with ST in transabdominal preperitoneal hernioplasty (TAPP) was performed at our department. The primary end point of our study was to assess the patient outcome by using a visual analog scale (VAS) and the short form 36 (SF-36). The evaluation of recurrence rates was the secondary aim. Methods: According to the randomization, a macroporous mesh (TiMESH) was fixed in group A (44 patients with 54 inguinal hernias) with FS (TISSEEL) or in group B (45 patients with 56 inguinal hernias) with ST (EMS Stapler). The observation period was 1 year with regular clinical check ups and assessment of VAS and SF-36. Results: Patient characteristics expressed by BMI, ASA scores, and Schumpelick hernia classification were similar in both treatment groups. In each group there was one recurrence within 8 (FS) and 9 months (ST) postsurgery. The mean preoperative pain values scored by VAS were 1.7 (range = 0-7.5) in the FS group and 2.2 (range = 0-6) in the ST group. Postoperative mean VAS scores measured at 1 year postsurgery were 0.4 (range = 0-3) in the FS group and 0.9 (range = 0-7.5) in the ST group. One year postsurgery there was no significant difference between the two groups with respect to the parameter pain in the SF-36 and VAS. Conclusion: Fibrin sealant fixation leads to a low rate of hernia recurrence and avoids tissue trauma. ST provide similar results in the hand of the expert but bear inherent risks of complications due to tissue perforation. [ABSTRACT FROM AUTHOR]

Copyright of European Surgery: ACA Acta Chirurgica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AZD1152 is a highly selective Aurora B kinase inhibitor currently undergoing Phase I and II clinical evaluation in patients with acute myelogenous leukemia and advanced solid malignancies. We have established two AZD1152-resistant cell lines from SW620 colon and MiaPaCa pancreatic carcinoma lines, which are >100-fold resistant to the active metabolite of AZD1152, AZD1152 HQPA and interestingly, cross-resistant to the pan-Aurora kinase inhibitor, VX-680/MK0457. Using whole-genome microarray analysis and comparative genomic hybridization, we were able to identify MDR1 and BCRP as the causative genes that underlie AZD1152 HQPA-resistance in these models. Furthermore, the upregulation of either of these genes is sufficient to render in vivo tumor growth insensitive to AZD1152. Finally, the upregulation of MDR1 or BCRP is predictive of tumor cell sensitivity to this agent, both in vitro and in vivo. The data provide a genetic basis for resistance to Aurora kinase inhibitors, which could be utilized to predict clinical response to therapy.The Pharmacogenomics Journal (2009) 9, 90–102; doi:10.1038/tpj.2008.20; published online 3 February 2009 [ABSTRACT FROM AUTHOR]

Small-molecule inhibitors of the Aurora A and B kinases interfere with mitotic centrosome function and disrupt the mitotic spindle assembly checkpoint resulting in polyploidization and apoptosis of proliferating cells. As such, several Aurora kinase inhibitors are at various stages of clinical development as anticancer agents. To identify candidate apoptosis-sensitizing genes that could be exploited in combination with Aurora kinase inhibitors in malignant glioma, we have carried out global gene expression analysis in a D54MG glioma cell derivative treated with three Aurora kinase inhibitors chosen for their distinctive selectivities: MLN8054 (Aurora A-selective), AZD1152 (Aurora B-selective), and VX-680 (Aurora A/B). The modulation of apoptotic gene expression by p53 under these conditions was ascertained, as p53 expression can be toggled on and off in this D54MG derivative by virtue of a stable, inducible, p53-targeting short hairpin RNA (D54MGshp53). This analysis identified the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor, TRAIL receptor 2 (TRAIL-R2), as an apoptosis-sensitizing gene induced selectively following inhibition of Aurora B. In glioma cell lines where TRAIL-R2 was induced following polyploidization, the sensitivity, kinetics, and magnitude of TRAIL-mediated apoptosis were enhanced. Our data shed light on the apoptotic program induced during polyploidization and suggest that TRAIL-R2 activation is a putative point of therapeutic intervention in combination with inhibitors of Aurora B.Cell Death and Differentiation (2009) 16, 498–511; doi:10.1038/cdd.2008.174; published online 12 December 2008 [ABSTRACT FROM AUTHOR]

Chronic pain is a major concern in open and laparoscopic hernia repair. Study groups have adopted a variety of tools to assess postoperative (postOP) pain and quality of life (QoL). Unfortunately, modifications of existing tests and self-designed questionnaires are common, yielding unvalidated results and making comparison of data difficult. The aim of this study was to assess the QoL in transabdominal preperitoneal mesh repair (TAPP) with fibrin sealant (FS) for lightweight mesh fixation, applying the standardised Short Form 36 (SF36) questionnaire in its unmodified design. The SF36 has already been validated and implemented in a large number of studies. In this trial the physical-health-component summary measure (PHM), summarising the physical health-related scales, served as the primary outcome parameter. After informed written consent was obtained, TAPP with fibrin mesh sealing was performed in 11 non-selected consecutive patients by a single surgeon. A direct control group (e.g. TAPP with staples) was not enrolled, because a favourable change in the QoL in patients subjected to the mesh sealing approach was the tested hypothesis and not the comparison of techniques. The macroporous mesh (TI-Mesh, GfE, Germany) was fixed with 1 ml of FS (FS, Tisseel, Tissucol, Baxter Biosciences, Austria), and the QoL and pain were assessed preoperatively and 1 year postOP using the SF36 survey and the visual analogue score (VAS). After 12 months, recurrences or complications were observed. The analysis of the unmodifed SF36 revealed a highly significant improvement in the PHM, based on significant changes of all physical-health-related scales. The scale ‘social functioning’ (SOCIAL), which belongs to the mental-health-related scale, had also significantly improved. The VAS was significantly reduced after 1 year. Despite a small number of patients ( n = 11), a strikingly significant improvement in physical health and reduction of pain was detected with the unmodified SF36 and the VAS 1 year after TAPP repair with fibrin-sealed lightweight meshes. We suggest the use of the unmodified SF36 for QoL in hernia repair in order to assess all aspects of recovery (physical and mental) and to facilitate comparison of data. [ABSTRACT FROM AUTHOR]

The proton nuclear magnetic resonance spin–lattice relaxation time has been successfully used to evidence the reorientation of the imidazolium rings in carboxylic acid salts of imidazole: imidazolium oxalate, imidazolium adipate monohydrate and diimidazolium suberate. The process occurs in the temperature range between 325 K and the melting point of the salts (523, 379 and 360 K) and is described by a single activation energy of 20, 48 and 66 kJ/mol for imidazolium oxalate, imidazolium adipate monohydrate and diimidazolium suberate, respectively. The studied salts are considered as possible candidate materials for fuel-cell membranes. [ABSTRACT FROM AUTHOR]

Internal tandem duplications (ITDs) of fms-like tyrosine kinase 3 (FLT3) receptor play an important role in the pathogenesis of acute myeloid leukemia (AML) and represent an attractive therapeutic target. ABT-869 has demonstrated potent effects in AML cells with FLT3-ITDs. Here, we provide further evidence that ABT-869 treatment significantly downregulates cyclins D and E but increases the expression of p21 and p27. ABT-869 induces apoptosis through downregulation of Bcl-xL and upregulation of BAK, BID and BAD. We also evaluate the combinations of ABT-869 and chemotherapy. ABT-869 demonstrates significant sequence-dependent synergism with cytarabine and doxorubicin in cell lines and primary leukemia samples. The optimal combination was validated in MV4-11 xenografts. Low-density array analysis revealed the synergistic interaction involved in downregulation of cell cycle and mitogen-activated protein kinase pathway genes. CCND1 and c-Mos were the most significantly inhibited targets on both transcriptional and translational levels. Treatment with short hairpin RNAs targeting either CCND1 or c-Mos further sensitized MV4-11 cells to ABT-869. These findings suggest that specific pathway genes were further targeted by adding chemotherapy and support the rationale of combination therapy. Thus, a clinical trial using sequence-dependent combination therapy with ABT-869 in AML is warranted. [ABSTRACT FROM AUTHOR]

Copyright of European Surgery: ACA Acta Chirurgica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Gastroesophageal reflux disease (GERD) is the most common foregut disease, with a great impact on quality of life and with intestinal, respiratory and cardiac symptoms and implications of carcinogenesis of the oesophagus. Medical therapy often fails, due to the complex pathophysiology of GERD. Surgery can cure the disease, since it is able to restore the anti-reflux barrier. It improves quality of life and prevents carcinogenesis. Methods: Review of the literature and presentation of our own experience and data in a series of more than 4,000 evaluated patients referred for suspected reflux disease, of whom 382 have been operated on. Conclusion: The laparoscopic Nissen fundoplication is the most commonly used operation technique. It provides good long-term results in the majority of patients. However, due to an increase of outflow resistance of the oesophagus this operation is associated with some postoperative side effects. Therefore, alternative anti-reflux procedures may be indicated in selected patients. [ABSTRACT FROM AUTHOR]

Presents the results of measurements of C[sub 2]-C[sub 12] nonmethane hydrocarbons during the BERLIOZ field experiment in July-August 1998 at different sites located in and around the city of Berlin, Germany. Site description; Survey of gas chromatographic systems used during the BERLIOZ campaign; Summary of benzene mixing ratios at the different stations with respect to winds from Berlin and from the west.

Presents the process analysis and numerical process simulation of the ozone and the peroxyacetyl nitrate (PAN) formation inside and outside of the Berlin plume in Germany in July and August 1998. Development of large-scale forcing and boundary layer in the Berlin area; Characteristics of the city plume; Analysis of processes involved in the city-plume formation.

Discusses the establishment of quality assurance in German Tropospheric Research Focus (TFS) which is aimed at the improvement of ozone forecast for inorganic compounds. Elements of quality assurance; Data quality objectives and procedures; Final data quality of Berlin Ozone Experiment measurements; Measurement systems used for oxides of nitrogen.

Background: Rectus sheath hematoma (RSH) is a rare entity that can mimic an acute abdomen. Therefore, we designed a study to analyze the etiology, frequency, diagnosis using ultrasound, and treatment of RSH.Methods: A total of 1,257 patients admitted for abdominal ultrasound for acute abdominal pain or unclear acute abdominal disorders were evaluated.Results: In 23 (1.8%) patients, an RSH was diagnosed; three of them were not diagnosed preoperatively by ultrasound. Of 13 men and 10 women (mean age, 57 +/- 23 years), 13 developed RSH after local trauma, three after severe coughing, two after defecation, and five spontaneously. Fifteen had nonsurgical therapy, and eight underwent surgery. The use of anticoagulants was accompanied by a larger diameter of the RSH (p <.012), and surgical therapy was more frequently required in these patients. In the surgically treated group, more intraabdominal free fluid could be detected by ultrasound (p <.0005), patients required less analgesics (p <.001), and the mean hospital stay was shorter (p <.001).Conclusions: RSH is a rare condition that is usually associated with abdominal trauma and/or anticoagulation therapy. Ultrasound is a good screening technique. Nonsurgical therapy is appropriate but leads to a greater need for analgesics. Surgery should be restricted to cases with a large hematoma or free intraabdominal rupture. [ABSTRACT FROM AUTHOR]

The renal actions of the optically active isomers of the new diuretic drug ozolinone were studied by clearance, flowmeter and micropuncture techniques in rats. The levorotatory, but not the dextrorotatory isomer of ozolinone increased urine flow, urinary sodium and chloride excretion and enhanced sodium and chloride concentrations in early distal tubular fluid as checked by in situ microperfusion of Henle's loops. This indicates stereospecifity of the drug's diuretic action. However, both isomers of ozolinone equally inhibited maximal tubular secretion of paraaminohippurate and increased renal blood flow as measured by an electromagnetic flowmeter. Thus, the different renal target structures of ozolinone differ markedly with respect to stereoselectivity. [ABSTRACT FROM AUTHOR]

The effect of several putative phospholipase A (PLA) inhibitors on [H]-acetate incorporation into platelet-activating factor (PAF) upon calcium ionophore A23187 stimulation of purified human neutrophils (PMN) were evaluated in vitro. PLA inhibitors such as p-bromophenacyl bromide ( pBPB), ellagic acid, aristolochic acid and gossypol were without effect or only weakly inhibited PAF biosynthesis. Luffariellolide, a potent PLA inhibitor isolated from the marine sponge Luffariella sp., dose-dependently inhibited PAF production (IC=5 μ M). Due to the relationship between PAF and LTB biosynthesis, the effect of inhibiting LTB production on PAF biosynthesis was investigated. At concentrations which reduce LTB production by >95%, Wy-50,295 tromethamine and A-64,077, specific 5-lipoxygenase (5-LO) inhibitors, did not significantly effect PAF production. In contrast, L-663,536, the 5-LO translocation inhibitor, was a potent inhibitor of PAF production (IC=1 μ M). This activity of L-663, 536 may contribute to its pharmacological profile at higher doses. These data also suggest that PAF biosynthesis in human PMNs is not dependent on the formation or continued presence of leukotrienes. [ABSTRACT FROM AUTHOR]

According to the literature synchronous adenocarcinomas of both, the colon and the gallbladder or the colon and the appendix are extremly unusual. To our knowledge the simultaneous occurrence of all three tumors has never been published before. Preoperative diagnosis of early stage tumors of the gallbladder and the vermiform appendix is also made very seldom. The following case report records an instance of synchronous adenocarcinomas of the gallbladder, the transverse colon, in a colonic polyp and the appendix. Owing to the patient's advanced age simultane cancer occurrence may be mere coincidence. Nevertheless, this extremely rare entity could also be ascribed to a genetic defect or an unknown carcinogenic agent. [ABSTRACT FROM AUTHOR]

Objective and Design: To determine whole blood levels of sirolimus, a macrolide antibiotic in the rat developing adjuvant arthritis (AA) model after dosing orally with two different vehicles, and whether combinational doses of sirolimus and cyclosporin A (CsA) produced additive or synergistic inhibitory effects in this model.¶ Material: Male Lewis rats (150-180g).¶ Treatment: Arthritis was induced by the injection (0.5 mg/rat) of heat-killed Mycobacterium butyricum suspended in light mineral oil. Drugs were administered orally either in fine suspension (0.5% Tween 80) or in emulsion (phosal 50 PG in 1% Tween 80) at doses of 0.1 to 5 mg/kg in a 7 day, MWF or daily regimen.¶ Method: Paw volumes (ml) were measured by automated mercury plethysmograph and sirolimus concentrations in whole blood were quantitated by liquid chromatography/mass spectroscopy.¶ Results: At 72 h (7 days after adjuvant) after receiving the third oral dose (4.5 mg/kg p.o.), the phosal vehicle resulted in higher sirolimus blood levels (2.5 ng/ml) than in Tween 80 (1.6 ng/ml). After the rats received the last oral dose on day 14, (7 total doses of sirolimus at 4.5 mg/kg) the sirolimus blood levels (2 h after the last dose) were about 2 times higher for the phosal dosed rats (9.8 ng/ml) compared to Tween 80 dosed rats (4.6 ng/ml). Even 24 h after the last dose, sirolimus blood levels were still elevated in the phosal dosed rats (0.8 ng/ml) relative to 0.5% Tween 80 dosed rats (0.5 ng/ml). At day 16 in the rat developing model, sirolimus, when given in phosal vehicle, produced an ED50 of 0.28 mg/kg (i.e. inhibition of uninjected paw edema) that was about 5.5 times lower than using 0.5% Tween 80 as the suspending agent (ED50 = 1.6 mg/kg). When combining sirolimus and CsA using precalculated doses for producing an additive effect in this adjuvant model, an additive inhibitory effect on uninjected paw edema was observed at equal combinational doses of 0.5 and 2 mg/kg, respectively.¶ Conclusions: The phosal vehicle used in administering sirolimus increases the absorption and whole blood levels in the rat and the elevated blood levels correlated positively with the therapeutic effect in the rat developing AA model. In addition, combination therapy using sirolimus and CsA produced an additive effect in rat developing AA. [ABSTRACT FROM AUTHOR]

Partial posterior fundoplication improves esophageal peristalsis in patients with gastroesophageal reflux disease (GERD) associated with poor esophageal body function. The aim of this study was to investigate whether postoperative administration of cisapride enhances the effect of surgery on esophageal peristalsis. Laparoscopic partial posterior fundoplication was performed on 34 consecutive GERD patients with poor esophageal body motility. These patients were randomized in groups without and with postoperative treatment with cisapride 20 mg twice daily for six months. Esophageal manometry was performed preoperatively and six months following surgery. Esophageal body function improved significantly following partial posterior fundoplication without or with postoperative treatment with cisapride. However, this effect was more pronounced in the group of patients receiving cisapride. Partial posterior fundoplication combined with postoperative treatment with cisapride should be the therapy of choice in GERD patients with poor esophageal body motility. [ABSTRACT FROM AUTHOR]

Copyright of e & i Elektrotechnik und Informationstechnik is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sigmoid volvulus commonly presents with signs of bowel obstruction. In the absence of an exact preoperative diagnosis, these patients have to undergo urgent surgery. We report a case of sigmoid volvulus diagnosed radiologically and managed by endoscopic derotation. When the cause of the obstruction is known to be due to sigmoid volvulus, surgery can be avoided by careful endoscopic derotation of the sigmoid colon. [ABSTRACT FROM AUTHOR]

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Luffariellolide ( 2) is a sesterterpene from the Palauan sponge Luffariella sp. that has useful anti-inflammatory properties. In contrast with the irreversible action of manoalide ( 1) on phospholipase A, luffariellolide ( 2) is a slightly less potent but partially reversible PLA inhibitor. [ABSTRACT FROM AUTHOR]

WAY-121,520 inhibited human synovial fluid PLA (HSF-PLA) (IC=4 μ M) using arachidonic acid-labeled E. coli as substrate. Further biochemical characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase (5-LO) activity in the murine macrophage (LTC, IC=4n M) and rat PMN (LTB, IC=10 n M) and an ability to antagonize LTD binding to isolated guinea-pig trachea (p K=6.0). In vivo anti-inflammatory activity was noted in murine TPA-induced (ED=91 μg/ear) and arachidonic acid-induced (66% inhibition at 400 μg/ear) ear edema and in leukotriene-dependent antigen-induced bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY-121,520 represents a novel series of indomethacin-based inhibitors of PLA with anti-inflammatory activity resulting from a combination of biochemical activities (inhibition of 5-LO and PLA and LTD antagonism). This agent may provide added therapeutic efficacy over more selective inhibitors. [ABSTRACT FROM AUTHOR]

We were intrigued by reports of the inhibition of phospholipase A (PLA) by indomethacin. In order to increase the potency of the indomethacin system as an inhibitor of PLA, it was decided to make more lipophilic analogs. Indeed, covalent attachment of a quinoline ring to the methoxy substituent of indomethacin affords WAY-122,220 which is almost an order of magnitude more potent than indomethacin in inhibiting human synovial fluid PLA (IC=15 and 145 μ M, respectively). The N−p-chloro-benzyl analog of this compound, WAY-121,520, was an even more potent inhibitor of PLA (IC=4 μ M). Structural analyses and molecular modeling suggest that these compounds may inhibit PLA by mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis inhibitor both in the rat PMN and mouse macrophage assays (IC=10 and 4 n M, respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its favorable anti-inflammatory profile. [ABSTRACT FROM AUTHOR]

Intraperitoneal injection of lipopolysaccharide (LPS) was used to elicit a sublethal, shock-like condition in mice. LPS, 2.5 mg/kg i.p., induced hypothermia, elevated serum TNF-α levels and lethality over a 48 h period in male CD-1 mice. The 5-lipoxygenase (LO) inhibitors, WY-50,295 tromethamine and zileuton (100 mg/kg p.o), significantly inhibited hypothermia at 4, 24 and 48 h after LPS. Interestingly, whereas cyclooxygenase (CO) inhibitors (ibuprofen, etodolac, naproxen and tenidap) at 40-80 mg/kg p.o. stimulated hypothermia at 4 h, they significantly reduced the later stages of hypothermia at 24-48 h. Rolipram (PDE-IV inhibitor) and dexamethasone significantly reduced hypothermia at 4-24 h and 1-24 h, respectively. All the anti-inflammatory agents significantly reduced elevated TNF-α levels at ∼70 min post-LPS, except for ibuprofen. In conclusion, these anti-inflammatory standards indicate that LPS-induced shock involves multiple lipid mediators (PG's, LT's and possibly PAF) and secondary cytokine generation. This sublethal model of LPS-induced shock represents a sensitive model for estimating the efficacy of potential drug candidates for the treatment of endotoxic shock. [ABSTRACT FROM AUTHOR]

The effectiveness of an H+H-prophylaxis against perioperative acute pseudoallergic reactions in which histamine is involved, and against postoperative complications the incidence of which may be increased by these reactions, was the central problem of a randomized trial in 162 aged patients during elective conventional cholecystectomy. As main endpoint it was planned to use the systemic histamine release reaction, as it already had been defined for the conscious and anaesthetized human subject. However, it had to be reassessed and redefined for the intraoperative period after improvement of the plasma histamine assay and new findings about stress-induced histamine release and the kinetics of histamine release during certain phases of operation. Intraoperative release is, at present, defined solely as an increase of plasma histamine values after a particular action (phase of operation). It includes criteria concerning plasma histamine changes either in comparison to the base value before surgery or to the preceding value before the last surgical action. Histamine elevations must exceed the last value by more than 3 standard deviations of the analytical error (i.e. 200% if value <0.25 ng/ml and 40% above). Basic requirements for the histamine assay (quality control), correct sample taking and appropriate preparation have to be fulfilled over the whole trial period. When these criteria were applied to the 162 patients an overall incidence of histamine release during cholecystectomy of 55.6% was found with 9.7-20% during an individual phase of operation. The data of this study, performed under routine conditions, with a sufficient number of patients with elevated risk and event controlled plasma histamine values, lead to a better understanding of intraoperative histamine release, its incidence and extent. [ABSTRACT FROM AUTHOR]