6-ketoprostaglandin-f1-alpha and Peritonitis

6-ketoprostaglandin-f1-alpha has been researched along with Peritonitis* in 17 studies

Other Studies

17 other study(ies) available for 6-ketoprostaglandin-f1-alpha and Peritonitis

ArticleYear
Early vascular permeability in murine experimental peritonitis is co-mediated by resident peritoneal macrophages and mast cells: crucial involvement of macrophage-derived cysteinyl-leukotrienes.
    Inflammation, 2002, Volume: 26, Issue:2

    The initial phase of zymosan-induced peritonitis involves an increase of vascular permeability (peak at 30 min) that is correlated with high levels of vasoactive eicosanoids, namely, prostaglandins (PGI2 and PGE2) of cyclooxygenase-1 origin (as estimated by RT-PCR) and cysteinyl-leukotrienes. Previously, we showed that the increase of vascular permeability can be attributed only partially to mast cells and their histamine, as seen in mast cell-deficient WBB6F1-W/Wv mice. Thus we aimed to identify the major cellular source(s) that mediate vasopermeability, as well as particular vasoactive mediators operating in this model. For this purpose, some mice were selectively depleted of either peritoneal macrophages or mast cells, and/or they were treated with several pharmacologic inhibitors of cyclooxygenase- and lipoxygenase-metabolic pathways. More-over, macrophage-depleted mast cell-deficient WBB6F1-W/Wv mice and their controls (+/+) were used. The macrophage depletion always caused a profound decrease of both vascular permeability and lipid-mediator levels, which was particularly pronounced for leukotrienes, whereas the effects of mast-cell depletion were less severe. The macrophage/mast-cell co-mediation of vasopermeability was also revealed in thioglycolate-induced peritonitis, as well as the macrophage origin of cysteinyl-leukotrienes. Taken together, these findings demonstrate that the resident peritoneal macrophages are in fact the main contributors to the vasopermeability at the early stages of zymosan-induced peritonitis.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capillary Leak Syndrome; Capillary Permeability; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cysteine; Diterpenes; Eicosanoids; Enzyme Induction; Ginkgolides; Histamine Release; Indoles; Indomethacin; Isoenzymes; Lactones; Leukotriene C4; Leukotrienes; Lipoxygenase Inhibitors; Macrophages, Peritoneal; Male; Mast Cells; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Nitrobenzenes; Peritonitis; Phospholipid Ethers; Platelet Activating Factor; Prostaglandin-Endoperoxide Synthases; Quinolines; Sulfonamides; Thioglycolates; Zymosan

2002
Effect of indomethacin on peritoneal protein loss in a rabbit model of peritonitis.
    Kidney international, 2001, Volume: 59, Issue:1

    Although various inflammatory mediators have been previously shown to be released into the peritoneal cavity during peritonitis in peritoneal dialysis patients, those that are involved in governing changes in peritoneal permeability to small solutes and protein remain incompletely defined.. We determined the importance of prostanoid production in the enhanced protein loss observed during acute peritonitis by inhibition experiments using indomethacin, an inhibitor of cyclooxygenase activity. The association between changes in peritoneal permeability and the generation of inflammatory mediators after adding Escherichia coli to peritoneal dialysate was first examined in series 1 experiments. Series 2 experiments then determined the effect of intraperitoneal administration of indomethacin (75 microg/mL) on changes in peritoneal permeability after adding E. coli to peritoneal dialysate. All experiments were performed in male New Zealand White rabbits (2.6 to 3.4 kg body weight) using an eight-hour dwell of dialysate containing 2.5% glucose. Peritoneal permeability to creatinine and protein was assessed by time-dependent changes in the dialysate to plasma concentration ratios of these solutes.. Series 1 experiments showed enhanced leukocyte migration into the peritoneal cavity and increased peritoneal permeability to protein during bacterial challenge that was accompanied by an increase in the dialysate concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and interleukin-8, but not nitrate + nitrite (a measure of local nitric oxide production). Inhibition of prostanoid production by intraperitoneal administration of indomethacin in series 2 experiments resulted in lower dialysate concentrations of PGE2 and 6-keto-PGF1alpha and in lower peritoneal permeability to protein, both to control levels. No effect of indomethacin on transperitoneal migration of leukocytes or the generation of interleukin-8 was observed.. Enhanced production of prostanoids likely plays an important role in governing the increase in peritoneal permeability to protein during acute, bacterial peritonitis in the rabbit.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cell Movement; Cyclooxygenase Inhibitors; Dialysis Solutions; Dinoprostone; Escherichia coli Infections; Indomethacin; Injections, Intraperitoneal; Interleukin-8; Leukocytes; Male; Peritoneum; Peritonitis; Prostaglandins; Proteins; Rabbits

2001
Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis, 1995, Volume: 15, Issue:2

    To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis.. CAPD patients with a high peritonitis incidence stored every night bag at 4 degrees C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNF alpha, IL-6, PGE2, 6-keto-PGF1 alpha, TxB2, and serum proteins. The clearance of beta 2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient.. Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 x 10(6)/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of beta 2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNF alpha and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery.. In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNF alpha and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms.

    Topics: 6-Ketoprostaglandin F1 alpha; beta 2-Microglobulin; Blood Proteins; Dinoprostone; Female; Humans; Interleukin-6; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Permeability; Tumor Necrosis Factor-alpha

1995
Relationship of TNF-alpha, interleukin-6, and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis.
    The Journal of laboratory and clinical medicine, 1993, Volume: 122, Issue:6

    Infectious reactions are known to comprise changes in vasopermeability and inflammatory mediators. We used peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD) as an in vivo inflammation model to study the time courses of peritoneal permeability characteristics and mediators in dialysate. Sixteen episodes of peritonitis were prospectively followed on eight consecutive days from the onset of the infection and once after recovery (control). Dialysate night dwells were examined for marker proteins of peritoneal permeability, cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and prostaglandins (PGE2, 6-keto-PGF1 alpha, and thromboxane B2 [TxB2]). The clearance of beta 2-microglobulin was used as indicator of the effective peritoneal surface area. The intrinsic permeability was characterized functionally by the peritoneal restriction coefficient. All protein clearances were increased during the acute phase of peritonitis and subsequently decreased to control. Likewise, the intrinsic peritoneal permeability was elevated, as demonstrated by a decrease of the peritoneal restriction coefficient. Peritoneal appearance rates of TNF-alpha, IL-6, and prostaglandins were also increased during the acute phase. Peak values were reached on day 1. The largest increase was observed for IL-6 (median 854-fold), followed by TNF-alpha (35-fold). The vasodilating PGE2 and 6-keto-PGF1 alpha were increased 12-fold and the vasoconstricting TxB2 was increased threefold. Evidence was obtained for local intraperitoneal synthesis of IL-6 and prostaglandins. TNF-alpha production appeared to be present only during the early acute inflammatory response. Analysis of variance for repeated measurements revealed that changes in the clearance of beta 2-microglobulin were related to those in IL-6 and marginally also to TNF-alpha in dialysate. Changes in the peritoneal restriction coefficient were also related to IL-6, but were more closely related to alterations in dialysate PGE2. These findings suggest that TNF-alpha, IL-6, and PGE2 are involved in the changes in permeability characteristics during CAPD-related peritonitis.

    Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; beta 2-Microglobulin; Dinoprostone; Female; Humans; Interleukin-6; Kinetics; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Permeability; Prostaglandins; Thromboxane B2; Tumor Necrosis Factor-alpha; Vasodilation

1993
A comparison of the anti-inflammatory activity of selective 5-lipoxygenase inhibitors with dexamethasone and colchicine in a model of zymosan induced inflammation in the rat knee joint and peritoneal cavity.
    Agents and actions, 1991, Volume: 32, Issue:3-4

    Intraperitoneal and intra-articular (knee joint) injection of zymosan in the rat caused two phases of increased vascular permeability, a rapid increase (0.25-0.5 h) and a secondary increase (2-3 h) which was temporally associated with the onset of leukocyte infiltration. Intraperitoneal injection of zymosan led to a single peak of eicosanoid production (LTB4, C4, D4, E4 and 6-oxo-PGF1 alpha) which was maximal at 0.125-0.25 h. Intra-articular injection led to an initial peak of LTB4 production (maximal at 0.25 h) and a secondary peak of LTB4 and PGE2 production (maximal at 3 h). Oral administration of the 5-lipoxygenase (5-LO) inhibitors phenidone, BW A4C (N-hydroxy-N-[3-(3-phenoxyphenyl)-2-propenyl] acetamide), A63162 (N-hydroxy-N-[1-(4-(phenylmethoxy) phenyl)ethyl] acetamide and ICI 207 968 (2-[3-pyridylmethyl]-indazolinone inhibited LTB4 production in A23187 stimulation blood ex vivo. The glucocorticosteroid dexamethasone had no effect in this model. The initial phase of increased vascular permeability in the peritoneal cavity and LTB4 production was dose dependently inhibited by the 5-LO inhibitors phenidone, BW A4C, A63162, and ICI 207 968 but not by dexamethasone or colchicine. The initial phase of increased permeability in the joint was unaffected by phenidone, BW A4C, dexamethasone or colchicine. However the latter two drugs inhibited the later phase of increased permeability and leukocyte infiltration in the joint and peritoneal cavity. These results demonstrate that zymosan induces eicosanoid production in vivo but the relative importance of these mediators varies depending on the inflammatory site.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arthritis; Benzeneacetamides; Calcimycin; Colchicine; Dexamethasone; Dinoprostone; Disease Models, Animal; Hydroxamic Acids; Inflammation; Kinetics; Knee Joint; Leukocytes; Leukotriene B4; Leukotrienes; Lipoxygenase Inhibitors; Male; Peritonitis; Pyrazoles; Rats; Zymosan

1991
Ibuprofen therapy in experimental porcine gram-negative septic shock.
    Resuscitation, 1991, Volume: 22, Issue:1

    To evaluate the effects of ibuprofen on gram-negative septic shock, immature piglets were subjected to fecal-Escherichia coli peritonitis. Group I (n = 5) received a 12.5 mg/kg bolus of ibuprofen in 0.9% benzyl alcohol, followed by a continuous infusion of 6.25 mg/kg/h. Group II (n = 5) received the vehicle, benzyl alcohol, and Group III (n = 5) received lactated Ringer's solution. Mean survival times among the three groups were not significantly different. Ibuprofen-treated animals had a mean survival time (+/- S.E.M.) of 17.1 +/- 2 h vs. 19.2 +/- 2.4 h in the benzyl alcohol group and 15.7 +/- 2.7 h in the animals receiving lactated Ringer's solution. Thromboxane B2 levels were not significantly different in the treatment vs. non-treatment groups while 6-keto-PGF1a levels were significantly lower in the ibuprofen-treated animals. Neutropenia and thrombocytopenia were not prevented by treatment with ibuprofen.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Escherichia coli Infections; Ibuprofen; Leukocyte Count; Peritonitis; Platelet Count; Pulmonary Circulation; Shock, Septic; Swine; Thromboxane B2; Vascular Resistance

1991
The antinociceptive activity of paracetamol in zymosan-induced peritonitis in mice: the role of prostacyclin and reactive oxygen species.
    British journal of pharmacology, 1990, Volume: 101, Issue:4

    1. Oral administration of high doses of paracetamol (600 mg kg-1 or more) resulted in inhibition of the writhing and reduced the levels of prostacyclin (PGI2, measured as 6-keto-PGF1 alpha) induced by intraperitoneal administration of zymosan in mice. The high oral doses of paracetamol required were accompanied by behavioural toxicity which may have contributed to the inhibition of writhing. 2. The number of writhes per mouse and the proportion of mice writhing at least once correlated significantly with the levels of 6-keto-PGF1 alpha. However, inhibition of writhing by paracetamol occurred at higher levels of 6-keto-PGF1 alpha than was previously observed with acidic non-steroidal anti-inflammatory agents. 3. When injected i.p., PGI2, carbacyclin and iloprost (agonists at the PGI2 receptor) induced writhing. Intraperitoneal injection of PGI2 reversed the inhibition of writhing induced by indomethacin (1 mg kg-1, p.o.) but not that induced by oral administration of paracetamol. 4. Paracetamol at 800 mg kg-1, p.o., inhibited carbacyclin-induced writhing but indomethacin at 1 mg kg-1 p.o. did not. Paracetamol administered i.p. at 100 mg kg-1 reduced the peritoneal levels of 6-keto-PGF1 alpha and inhibited zymosan-induced but not carbacyclin-induced writhing and did not produce behavioural toxicity. 5. The in vitro potency of paracetamol as a prostaglandin synthesis inhibitor is known to be reduced by the presence of lipid peroxides. However, no lipid peroxides, measured as thiobarbituric acid reactive material, were detected in the peritoneal lavage fluid of zymosan-injected mice. 6. Intraperitoneal administration of a mixture of superoxide dismutase and catalase reduced detectable superoxide anion by 98% without inhibiting the writhing response to zymosan or the antinociceptive potency of paracetamol. 7. The data are consistent with the suggestion that inhibition of PGI2 synthesis in the peritoneal cavity by paracetamol is responsible for only a part of its antinociceptive activity in this test. However, extremely high oral doses of paracetamol were required which produced behavioural toxicity which clearly contributed to the inhibition of writhing. The low potency of paracetamol in this model cannot be attributed to the generation of lipid peroxides via the oxidative burst.

    Topics: 6-Ketoprostaglandin F1 alpha; Acetaminophen; Analgesics; Animals; Dinoprostone; Epoprostenol; Free Radicals; Iloprost; Lipid Peroxides; Luminescent Measurements; Macrophages; Male; Mice; Peritonitis; Platelet Aggregation Inhibitors; Superoxides; Zymosan

1990
Vasoactive hormones in the renal response to systemic sepsis.
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 1988, Volume: 11, Issue:1

    The pathophysiology of renal dysfunction in generalized sepsis remains unknown. In this study, 24 hours after surgical induction of peritonitis in 20 volume-loaded sheep, three patterns of renal function were seen. In group 1 (n = 8), glomerular filtration rate (GFR) decreased by 70%, urine volume by 85%, absolute sodium excretion by 95%, and fractional sodium excretion by 83%. Group 2 (n = 4) exhibited similar sodium retention but GFR did not fall. Group 3 (n = 8) showed no change in GFR or urine volume and only minimally reduced sodium excretion. Mean arterial pressure fell 17% in group 1 only; central venous pressure, pulmonary capillary wedge pressure, and plasma volume were maintained at or above presepsis values in all groups. Cardiac index was either increased or unchanged, and renal plasma flow was maintained in all groups; there was thus no hemodynamic evidence to suggest volume contraction. Histologic examination showed only minor changes with no consistent pattern. Renal functional changes correlated with other manifestations of severe sepsis--GFR and sodium retention correlated significantly with increased cardiac index, decreased systemic vascular resistance, pulmonary arterial hypertension, leukopenia, hypoproteinemia, and hypoglycemia. All of these changes were most marked in group 1. In groups 1 and 2, plasma renin activity (PRA) increased and urinary kallikrein excretion decreased. PRA correlated inversely with GFR, urine volume, and sodium excretion; urinary kallikrein excretion correlated positively with urine volume and sodium excretion. Urinary excretion of 6-keto-PGF1 alpha was increased in groups 1 and 2 and correlated inversely with mean arterial pressure in group 1 animals. During sepsis, urinary thromboxane B2 excretion continued at presepsis values in all groups. The results suggest that unusual reciprocal changes in activity of the renin-angiotensin and renal kallikrein-kinin systems may play a role in the renal response to sepsis. PGI2 synthesis is increased and may affect systemic hemodynamics and renal function; the role of thromboxane A2 in this context is unknown.

    Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Animals; Glomerular Filtration Rate; Hemodynamics; Kallikreins; Kidney; Kinins; Natriuresis; Peritonitis; Prostaglandins; Renin; Renin-Angiotensin System; Sheep; Thromboxane B2

1988
The clinical significance of prostaglandins and thromboxane as mediators of septic shock.
    Klinische Wochenschrift, 1987, Jan-15, Volume: 65, Issue:2

    An evaluation was made of 106 surgical patients with Gram-negative septic shock, both for clinical criteria as well as the biochemical mediators endotoxin, prostaglandin F2 alpha, prostaglandin I2 (prostacyclin), and thromboxane. These data were correlated to various defined shock phases, functional data of vital organs, and clinical outcome. Patients underwent invasive organ function monitoring and the usual laboratory tests of intensive care. Prostaglandins and thromboxane were measured radioimmunologically, endotoxin by the limulus amebocyte lysate test. Endotoxin proved to be a more accurate predictor of severe sepsis than did positive blood cultures. Endotoxin as well as prostaglandins and thromboxane are predominantly released in early shock phases, appearing in plasma concentrations, which correlate with the severity of organ failure. Sepsis-induced respiratory failure coincides with a deterioration of pulmonary prostaglandin inactivation, which contributes to the release mechanism. High systemic prostacyclin activity benefits the patients' organ functions and clinical outcomes, while a predominance of thromboxane seems to effect the opposite. Transpulmonary-thromboxane gradients correlate significantly with pulmonary hypertension in the early phases of septic shock.

    Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Adolescent; Adult; Aged; Dinoprost; Endotoxins; Epoprostenol; Humans; Middle Aged; Peritonitis; Prostaglandins; Prostaglandins F; Respiratory Insufficiency; Shock, Septic; Surgical Wound Infection; Thromboxanes

1987
Immune complex mediated inflammation in the mouse peritoneal cavity. A method for investigating inhibitors of arachidonate metabolism.
    Journal of pharmacological methods, 1986, Volume: 15, Issue:1

    Intraperitoneal injection of washed, preformed ovalbumin/anti-ovalbumin immune complexes caused the production of slow-reacting substance (SRS), prostaglandin E2, 6 keto prostaglandin Fla, vascular permeability (measured as extravazation of pontamine sky blue injected previously into the bloodstream), and polymorphonuclear leukocyte (PMN) infiltration in the mouse peritoneal cavity. Arachidonic acid metabolites appeared early in the response at 7.5 min; dye extravazation and PMN infiltration peaked at 30 min and 4 hr, respectively, after immune complex injection. BW755C and phenidone given orally 30 min before immune complex injection inhibited dye extravazation and SRS formation at 7.5 and 30 min. Indomethacin by the same regimen inhibited dye extravazation at 7.5 min but not at 30 min, while enhancing SRS formation at both times. Dexamethasone inhibited dye extravazation and to some extent SRS formation at both times. The data suggests that the mouse model may be useful for demonstrating an antiinflammatory activity of dual inhibitors that is clearly distinguishable from the activities shown by classical nonsteroidal antiinflammatory drugs and steroids.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antigen-Antibody Complex; Arachidonic Acid; Arachidonic Acids; Dinoprostone; Eicosanoic Acids; Female; Male; Mice; Peritonitis; Prostaglandins; Prostaglandins E; Rabbits; SRS-A; Time Factors

1986
Prostaglandin-mediated loss of proteins during peritonitis in continuous ambulatory peritoneal dialysis.
    Kidney international, 1986, Volume: 29, Issue:2

    The loss of proteins into the dialysate and the peritoneal generation of the immunoreactive prostanoids PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and TXB2 were studied in 12 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) during 16 episodes of peritonitis and in inflammation-free periods. Protein permeability, defined as the ratio of dialysate/plasma protein (D/P), decreased with increasing molecular weight, independent of the condition of the peritoneum. With peritonitis a general rise of permeability was noticed for total protein (TP) and the individual proteins beta 2-microglobulin (beta MG), albumin (Alb), immunoglobulin G (IgG), and alpha 2-macroglobulin (alpha MG) (P less than 0.001). Simultaneously, an increase of dialysate prostanoids occurred with predominance of the vasodilative acting prostaglandins PGI2, determined as its metabolite 6-keto-PGF1 alpha, and PGE2 by factors of 8.4 and 9.7, respectively (P less than 0.001), in comparison to peritonitis-free control. In the early phase of peritonitis (0 to 12 hr after the onset of therapy) the augumented peritoneal prostaglandin synthesis correlated positively with the increased permeability of TP (r greater than or equal to 0.7446, P less than 0.01) and the individual proteins beta MG, Alb, IgG, and alpha MG (r greater than or equal to 0.5970, P less than 0.05). Inhibition of cyclo-oxigenase activity by local administration of indomethacin inhibited both the generation of 6-keto-PGF1 alpha and PGE2 by 39 and 42%, respectively (P less than 0.05), and the peritoneal loss of TP by 34% (P less than 0.05). In the absence of peritonitis indomethacin only diminished the synthesis of PGE2 whereas the generation of the other prostanoids remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Dinoprost; Dinoprostone; Female; Humans; Indomethacin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Permeability; Prostaglandins; Prostaglandins E; Prostaglandins F; Proteins; Thromboxane B2

1986
Infectious-inflammatory changes in cyclic AMP levels and in their regulation by prostaglandins in human peritoneal macrophages.
    Prostaglandins, leukotrienes, and medicine, 1985, Volume: 18, Issue:2

    Peritoneal macrophages of renal patients on continuous ambulatory peritoneal dialysis (CAPD) have been collected when CAPD was without complications, during an intercurrent infectious peritoneal inflammation and after recovery. Levels of cyclic AMP, release of cyclo-oxygenase metabolites, and responsiveness, in terms of cyclic AMP elevation, to either PGE2 or to DC-PGI2 (a stable analogue of PGI2) were examined. Peritoneal inflammation was associated with a sharp drop in cyclic AMP, which was restored after recovery. Production of TXA2, PGI2 and PGE2 parallelled the direction of changes in cyclic AMP levels, except, that release of PGE2 entirely failed to recover. Macrophages during the uncomplicated stage of CAPD proved more responsive to DC-PGI2 than to PGE2. During inflammation the cells displayed a marked increase in sensitivity towards PG stimulation. Improved sensitivity was more pronounced with PGE2 than with DC-PGI2 and so the original difference between responsiveness of the cells to the PGs was abolished. Several findings are compatible with the view that endogenous PGI2 governs the cyclic AMP levels in human non-inflammatory peritoneal macrophages. However, during infectious-inflammation the cells undergo changes which render a reduced production of PGI2 insufficient to explain the drop in cyclic AMP.

    Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Cyclic AMP; Dinoprostone; Epoprostenol; Female; Humans; Inflammation; Macrophages; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prostaglandins E; Thromboxane B2

1985
Plasma levels of 6-keto PGF1 alpha but not TxB2 increase in rats with peritonitis due to cecal ligation.
    Circulatory shock, 1985, Volume: 16, Issue:3

    Acute, overwhelming sepsis or endotoxemia in experimental animals is associated with increased circulating levels of thromboxane (Tx)B2 (stable metabolite of TxA2) and 6-keto PGF1 alpha (stable metabolite of prostacyclin). The purpose of the present investigation was to determine the plasma prostanoid response to sepsis using an animal paradigm in which the septic process evolved more slowly than in previous similar studies. Bacterial peritonitis was induced in rats by cecal ligation (group B) or cecal ligation plus puncture with a 22-gauge needle (group C). Compared to sham-operated controls (group A), levels of immunoreactive 6-keto PGF1 alpha were significantly (p less than .05) elevated in group C rats at 6, 12, and 24 hr after surgery. At 48 hr after surgery, levels of this prostanoid were significantly (p less than .05) elevated in group B animals. In contrast, TxB2 levels were never significantly increased in septic (groups B and C) as compared to control (group A) rats. These data are consistent with results from several clinical studies and emphasize an important difference between the cecal ligation model and other experimental sepsis paradigms.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cecum; Ligation; Male; Peritonitis; Radioimmunoassay; Rats; Rats, Inbred Strains; Sepsis; Thromboxane B2; Time Factors

1985
Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock.
    Circulatory shock, 1985, Volume: 17, Issue:1

    Septic shock is associated with increased metabolism of arachidonic acid to thromboxane A2 (TxA2) and prostacyclin (PGI2). The effects of ibuprofen, methylprednisolone-sodium succinate, and gentamicin alone, or in combination on survival time and, TxA2 and PGI2 production in rats in a LD100 fecal peritonitis shock model were assessed. Plasma levels of TxA2 and PGI2 were measured by radioimmunoassay of their stable metabolites immunoreactive (i) TxB2 and i6-keto-PGF1 alpha, respectively. Drugs were given 30 min before induction of fecal peritonitis. Survival times in hours were as follows: fecal peritonitis = 10.5 +/- 0.4 (n = 50); ibuprofen (15 mg/kg) = 16.1 +/- 0.8 (n = 8); methylprednisolone-sodium succinate (40 mg/kg) = 17.1 +/- 0.7 (n = 22); methylprednisolone-sodium succinate (80 mg/kg) = 46.1 +/- 10.4 (n = 25) with 8% long-term survivors (survival greater than 7 days); gentamicin (4 mg/kg) = 23.8 +/- 4.4 (n = 16); methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 20.3 +/- 1.8 (n = 6); gentamicin + methylprednisolone-sodium succinate = 31.0 +/- 1.6 (n = 11); gentamicin + ibuprofen = 28.5 + 2.3 (n = 12); gentamicin + methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 46.9 +/- 5.4 (n = 8). Treatment with the combination of gentamicin + ibuprofen + methylprednisolone-sodium succinate (80 mg/kg) resulted in a mean survival time of 116 +/- 13.9 h with 26% long-term survivors. Methylprednisolone-sodium succinate (40 mg/kg) reduced (P less than 0.05) plasma iTxB2 from 995 +/- 78 (n = 16) to 714 +/- 48 (n = 18) pg/ml and i6-keto-PGF1 alpha from 4,090 +/- 334 (n = 12) to 2,009 +/- 119 (n = 17) pg/ml, 4 h post-FP. Methylprednisolone-sodium succinate (80 mg/kg) produced no further decrease in either iTxB2 or i6-keto-PGF1 alpha. Ibuprofen reduced the fecal peritonitis-induced iTxB2 and i6-keto-PGF1 alpha synthesis to nondetectable levels (less than 200 pg/ml). The latter results demonstrate that methylprednisolone-sodium succinate is less effective than ibuprofen in inhibiting arachidonic acid metabolism and suggest other salutary actions. These composite observations provide evidence that conjoint therapy with steroidal and nonsteroidal anti-inflammatory agents, and antibiotics in septic shock may be beneficial.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Disease Models, Animal; Drug Therapy, Combination; Female; Gentamicins; Ibuprofen; Indomethacin; Methylprednisolone; Peritonitis; Rats; Shock, Septic; Thromboxane B2

1985
Stimulation of peritoneal synthesis of vasoactive prostaglandins during peritonitis in patients on continuous ambulatory peritoneal dialysis.
    European journal of clinical investigation, 1985, Volume: 15, Issue:1

    The peritoneal generation of arachidonic acid metabolites was studied in eight patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD) during infection-free periods and during bacterial peritonitis. The prostacyclin metabolite 6-keto-PGF1 alpha was found to be the major prostanoid generated by human peritoneal mesothelium (1090 ng (6h)-1, SEM 86, n = 8) followed by lesser amounts of PGE2 (142 ng (6 h)-1, SEM 26, n = 8), PGF2 alpha (162 ng (6 h)-1, SEM 27, n = 8) and TXB2 (59 ng (6 h)-1, SEM 5, n = 8). During peritonitis a significant increase of all prostaglandins and TXB2 occurred (P less than 0.001). The ratio of the vasodilating prostaglandins and their metabolites (PGE2 and 6-keto-PGF1 alpha) to the vasoconstrictors and their metabolites (PGF2 alpha and TXB2) increased from 6.6 to 10.5 during peritoneal inflammation. Augmented peritoneal clearances of creatinin and urea and increased losses of proteins during peritonitis as well as the enhanced peritoneal generation of prostanoids were reduced to basal values by adequate antibiotic therapy. The present results suggest that the increased peritoneal blood flow during peritonitis, probably responsible for the observed changes of peritoneal transport properties, may be induced by a change in the ratio of vasoactive prostaglandins generated by peritoneal mesothelial cells.

    Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Dinoprost; Dinoprostone; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane B2

1985
Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis.
    Annals of surgery, 1984, Volume: 200, Issue:5

    This study investigates the role of prostaglandins (PG) in hyperdynamic sepsis. Thirteen chronically instrumented dogs were rendered septic by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. One day later, cardiac output (CO) increased from 2.80 +/- 0.22 to 3.72 +/- 0.32 l/min (p = 0.011); heart rate (HR) increased from 122 +/- 8 to 147 +/- 6 beats/min (p = 0.005); mean pulmonary artery pressure (PAP) increased from 15 +/- 1 to 19 +/- 1 mmHg (p = 0.003); mean systemic arterial pressure (MAP) decreased from 120 +/- 5 to 107 +/- 7 mmHg; and systemic vascular resistance (SVR) decreased from 44.1 +/- 2.6 to 29.3 +/- 1.9 mmHg/l/min (p less than 0.001). Sixty minutes after intravenous injection of indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), CO decreased to 2.60 +/- 0.21 l/min (p less than 0.001); HR decreased to 118 +/- 5 beats/min (p less than 0.001); PAP decreased to 17 +/- 1 mmHg (p = 0.021); and SVR increased to 43.7 mmHg/l/min (p less than 0.001). In seven control dogs, laparotomy alone did not significantly affect any of these parameters. Infusion of indomethacin caused a slight increase in MAP (106 +/- 4 to 116 +/- 4 mmHg, p = 0.035) but otherwise did not alter hemodynamics. It is concluded that administration of indomethacin or ibuprofen restores normal hemodynamics in a canine model of high-output sepsis, probably by inhibiting PG synthesis.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Disease Models, Animal; Dogs; Escherichia coli Infections; Female; Hemodynamics; Ibuprofen; Indomethacin; Male; Oxygen Consumption; Peritonitis; Prostaglandin Antagonists; Prostaglandins; Sepsis; Shock, Septic; Thromboxane A2

1984
Thromboxane and prostacyclin production during septic shock.
    Advances in shock research, 1982, Volume: 7

    We investigated a rat fecal peritonitis model of acute intraabdominal sepsis in order to evaluate the potential role of arachidonic acid metabolites in septic shock. Immunoreactive TxB2, the stable metabolite of thromboxane A2, and i6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Plasma levels of iTxB2 rapidly increased from nondetectable (ND less than 200 pg/ml) to 1,052 +/- 208 pg/ml, one hour after feces injection. iTxB2 then increased to 1,681 +/- 248 pg/ml at four hours and remained unchanged through six hours. Plasma i6-keto-PGF1 alpha increased from ND to 3,848 +/- 489 pg/ml a one hour. Four hours after feces, i6-keto-PGF1 alpha levels rose to 7, 450 +/- 933 pg/ml then continued to rise to 9,465 +/- 792 pg/ml at six hours. Either essential fatty acid deficiency (arachidonic acid depletion) or indomethacin treatment (cyclo-oxygenase inhibition) significantly decreased (P less than 0.01) the elevation of plasma iTxB2 and i6-keto-PGF1 alpha associated with fecal peritonitis. Thrombocytopenia occurred within six hours after injection of feces and was significantly improved (P less than 0.05) by indomethacin. Elevated fibrin degradation products at six hours (18 +/- 3 micrograms/ml) were significantly reduced in essential fatty acid-deficient (7 +/- 2 micrograms/ml; P less than 0.05) and indomethacin-treated (4 +/- 0.7 micrograms/ml; P less than 0.01) rats. Survival time (8.6 +/- 0.2 hours) was significantly enhanced by essential fatty acid-deficiency (10.2 +/- 0.4 hours; P less than 0.01) or indomethacin treatment (13.3 +/- 0.6 hours; P less than 0.01). These studies show that fecal peritonitis is associated with increased synthesis of thromboxane A2 and prostacyclin and suggest that these arachidonic acid metabolites may play a role in the pathophysiology of septic shock.

    Topics: 6-Ketoprostaglandin F1 alpha; Animals; Epoprostenol; Fatty Acids, Essential; Female; Fibrin Fibrinogen Degradation Products; Indomethacin; Peritonitis; Prostaglandins; Rats; Rats, Inbred Strains; Shock, Septic; Thrombocytopenia; Thromboxane A2; Thromboxanes; Time Factors

1982