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PubMed2001

Exacerbated inflammatory response induced by insulin-like growth factor I treatment in rats with ischemic acute renal failure.

In agreement with recent studies showing a deleterious effect of growth hormone treatment in critically ill patients, preliminary data showed that insulin-like growth factor I (IGF-I) administration increased the mortality rate of rats with ischemic acute renal failure (ARF). The present study was designed to investigate the mechanism responsible for this unexpected effect. Male rats with ischemic ARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (ARF+IGF-I, n = 5) or were untreated (ARF, n = 5). A group of 5 sham-operated rats were used as controls. Rats were killed 48 h after declamping, and the following studies were performed: in serum, creatinine and urea nitrogen; and in kidneys, histologic damage score, cellular proliferation by bromodeoxyuridine labeling, apoptosis by morphologic criteria, macrophage infiltration by immunohistochemistry using a specific antibody against ED-1, neutrophil infiltration by naphthol AS-D chloroacetate esterase staining, and levels of IGF-I and IGF-I receptor mRNA by RNase protection assay. ARF and ARF+IGF-I groups had a severe and similar degree of renal failure. Kidney damage was histologically more evident in ARF+IGF-I (1.9 +/- 0.1) than in ARF (1.3 +/- 0.2) rats, and the number of neutrophils/mm(2) of tissue was significantly greater in ARF+IGF-I than in ARF rats at the corticomedullary junction (52.3 +/- 5.2 versus 37.2 +/- 4.1) as well as at the renal medulla (172.5 +/- 30.0 versus 42.1 +/- 9.6). No other differences between the groups were found. It is concluded that IGF-I treatment enhanced the inflammatory response in rats with ischemic ARF. Cell toxicity derived from increased neutrophil accumulation might play a key role in the greater mortality risk of critically ill patients that are treated with growth hormone.

Acute Kidney Injury↗
PubMed1994

A simple method for screening assessment of skin and eye irritation.

A stepwise, simple screening test for skin and eye irritations, suitable for industrial chemicals or pesticides which are not required to be examined for their exact potential irritancy levels, was developed. The efficacy of the test was evaluated using 15 chemicals including typical irritants (acetic acid, ammonia, chloroacetic acid, dioxane, ethanolamine, formaldehyde, formic acid, hydrogen peroxide, phenol, phosphoric acid, propionic acid, sodium hydroxide, sodium hypochlorite, sulfuric acid, and trichloroacetic acid). Chemicals were chosen so as to represent irritants which act by different mechanisms (i.e., strongly acidic, alkaline, reactive to protein, oxidizing etc.). The method consisted of physicochemical tests and animal tests using rats, mice or guinea pigs, namely, a skin irritation test, an intradermal reaction test and an eye irritation test in a sequential manner such that further tests are not required if a positive result is obtained in earlier steps. Results obtained between two laboratories using this method were very similar. Comparison of our results with the data obtained by the conventional method using rabbits showed fairly good coincidence. The method was shown to be useful in assessing skin and eye irritation of chemicals and causes minimal suffering to animals.

Animals↗
PubMed1980

Metabolism of three active analogues of the male antifertility agent alpha-chlorohydrin in the rat.

1. Two ketal derivatives of alpha-chlorohydrin, which possess male antifertility activity, have been synthesized labelled with 36Cl. Both are metabolized by the rat to beta-chloroacetic acid. 2. Neither derivative inhibited the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and triosephosphate isomerase. 3. The epoxide glycidol is metabolized to beta-chlorolactic acid, presumably by first being converted to alpha-chlorohydrin. 4. It is proposed that the male antifertility actions of these three analogues is due to their biotransformation to alpha-chlorohydrin, which is then metabolized within mature sperm to a compound which is an inhibitor of glycolysis.

Animals↗
PubMed1991

Metabolism of 14C-dichloroethyne in rats.

1. The metabolism of 14C-dichloroethyne was studied in rats by inhalation in a dynamic nose-only exposure system. 14C-Dichloroethyne was generated in 95-99% yield from 14C-trichloroethene by alkaline dehydrochlorination. 2. After inhalation of 20 ppm and 40 ppm dichloroethyne for 1 h, the retention rates were 17.6% and 15.6% of the radioactivity introduced into the exposure system, respectively. During the period of observation (96 h), almost quantitative elimination of the dose was observed. Elimination with urine accounted for 60.0% (40 ppm) and 67.8% (20 ppm) of absorbed radioactivity and elimination with faeces for 27% (40 ppm) and 27.7% (20 ppm), 3.4-3.5% remained in the carcasses. 3. Metabolites of dichloroethyne identified are: N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, dichloroethanol, dichloroacetic acid, oxalic acid and chloroacetic acid in urine; N-acetyl-S-(1,2-dichlorovinyl-L-cysteine in faeces. 4. In bile of rats exposed to 40 ppm of dichloroethyne, S-(1,2-dichlorovinyl)glutathione was the only metabolite identified. Biliary cannulation did not influence the renal excretion of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, indicating that glutathione conjugate formation occurs in the kidney. 5. The results suggest that two metabolic pathways are operative in dichloroethyne metabolism in vivo. Cytochrome P450-dependent oxidation represents a minor pathway accounting for the formation of 1,1-dichloro compounds after chlorine migration. The major pathway is the biosynthesis of toxic glutathione conjugates. Organ-specific toxicity and carcinogenicity of dichloroethyne is due most likely to the topographical distribution of gamma-glutamyl transpeptidase which is concentrated mainly in the kidney in rats.

Acetylene↗
PubMed1979

Cytochemistry of esterases.

Esterases are enzymes that cleave aliphatic and aromatic ester bonds. With the use of synthetic substrates, esterases can be demonstrated in hematopoietic cells. Using alpha naphthyl acetate or alpha naphthyl butyrate, nonspecific esterase activity can be demonstrated. Intense activity of nonspecific esterase that is inhibited by fluoride is characteristic of cells of monocytic or reticulum cell origin. Using naphthol ASD-chloroacetate, specific esterase activity can be detected. Specific esterase is a lysosomal enzyme and is a useful marker for cells of granulocytic origin. Distinctive patterns of specific and nonspecific esterase activities are found in marrow cells from patients with various types of hematologic disorders. With the use of electrophoretic techniques, isoenzymatic analysis of esterases can be achieved.

Animals↗
PubMed2000

Clinical and biologic diversity of leukemias occurring in patients with mastocytosis.

Patients with systemic mast cell (MC) disease, but not those with cutaneous mastocytosis, are at a high risk (10-30%) to develop life-threatening myelogenous malignancies. In a significant proportion of cases, myeloid leukemias occur. Using conventional criteria, such leukemias resemble acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or myelomonocytic leukemia (CMML). Mast cell leukemia (MCL) may also occur. Myeloid leukemias (AML, CML, CMML) can develop in indolent or aggressive mastocytosis (skin lesions present or absent) with a variable prephase of MC disease. By contrast, MCL (typically without skin lesions) often develops on a "de novo" basis, and, if at all recognized, a prephase resembling (malignant) mastocytosis, is short. MCL differs from myeloid leukemias (AML, CML, CMML) by morphologic and phenotypic cellular characteristics. In fact, MCL are strongly tryptase-positive, c-kit-positive, myeloperoxidase (MPO) -negative neoplasms with variable metachromasia and chloroacetate esterase expression, whereas an MPO-positive, tryptase-negative phenotype supports the diagnosis of a myeloid non-MC lineage disease. Thus, MCL, but also myeloid non-MC lineage leukemias can develop in patients with (systemic) mastocytosis. Little is known, however, about the pathophysiologic basis of co-evolution. In the present article, the concomitant occurrence of mastocytosis and leukemia is discussed in the light of the literature and of concepts proposed to explain the biologic basis of this phenomenon.

Acute Disease↗
PubMed1993

Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH).

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Acute Disease↗
PubMed1993

The effects of benzene and hydroquinone on myeloid differentiation of HL-60 promyelocytic leukemia cells.

Chronic exposure of humans to benzene (BZ) affects hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and/or acute myelogenous leukemia and some of its variant forms. We studied the effects of BZ and hydroquinone (HQ), a toxic bone marrow metabolite, on the human HL-60 promyelocytic leukemic cell line. Because the HL-60 cell is bipotential and can be induced to differentiate to monocytes or granulocytes it has been used in many studies as a surrogate for the granulocyte/macrophage committed cell, GM-CFU. Treatment of HL-60 cells with BZ specifically induced differentiation along the granulocytic lineage as measured by morphology, induction of superoxide production and chloroacetate esterase activity and the appearance of the L12-2 surface antigen. Differentiation was induced via the activation of protein kinase C and the phosphorylation of several proteins known to be involved in HL-60 cell differentiation. Subsequent to kinase C activation, arachidonic acid was released from membrane phospholipids and the 5-lipoxygenase pathway was activated for the production of leukotriene D4 (LTD4) required for granulocytic differentiation. BZ induction of granulopoiesis was prevented by preincubation of HL-60 cells with inhibitors of protein kinase C, 5-lipoxygenase, gamma-glutamyl transpeptidase required for the conversion of LTC4 to LTD4, or LTD4 receptor antagonists. Treatment of HL-60 cells with tetraphorbol myristate acetate (TPA), 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH2)D3) or interleukin-1 (IL-1) induced HL-60 cells to differentiate to monocytes/macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonate 5-Lipoxygenase↗
PubMed1995

Recommended procedures for the classification of acute leukaemias.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Acute Disease↗
PubMed1981

Enzyme histochemistry on paraffin embedded tissue sections.

To obtain diagnostic enzyme reactions in paraffin embedded tissue sections, we compared four fixatives (buffered formol sucrose, Baker's formol calcium, periodate lysin paraformaldehyde, and buffered formalin acetone) and subsequent acetone dehydration with or without graded concentrations of Triton X-100. Four spleens and 14 lymph nodes were tested for peroxidase, naphthol ASD chloroacetate esterase, acid phosphatase, alpha naphthyl acetate esterase, and alpha naphthyl butyrate. Best results were obtained by a processing method using buffered formalin acetone, Holt's gum sucrose, dehydration in acetone with 0.03% Triton X-100, and paraffin for embedding.

Histocytochemistry↗
PubMed2003

[Acute myelocytic leukemia (M0) in an elderly patient with relapsed granulocytic sarcoma (M7) of bone during the second period of complete remission 5 years after onset].

A 75-year-old man was admitted because of right knee joint pain in December 1999. He had suffered from acute myelocytic leukemia (AML: M0) in November 1994 and achieved the first complete remission (CR) then. His AML relapsed in August 1996, but fortunately he achieved a second CR. Radiographical bone examination revealed osteolytic lesions in his right knee and bone scintigraphy showed uptake in the right knee and the middle part of the left femur. MRI also revealed a low attenuation signal in the left femur. He had no abnormal findings in peripheral blood or bone marrow. Histological examination of the biopsied bone tissue showed a diffuse proliferation of round cells with medium-sized or large nuclei. These cells were histochemistrically negative for myeloperoxidase and naphtol-ASD-chloroacetate esterase, and were also negative for lysozyme, cytokeratin 7, 9, 20, EMA, CEA, CD3, CD79a on immunohistochemistry, but were positive for CD43, CD56. In immunophenotypic analysis of these cells by flow cytometry, CD7, CD13, CD33, CD41, CD56 were revealed to be strongly positive. On the basis of these findings we diagnosed these tumors as granulocytic sarcomas (GS), extramedullary recurrence of AML M7. Although radiation (36Gy) to these tumors brought a temporary relief of the pain, he died of systemic relapse of AML in February 2001. When presented CD7+ AML M0 had been diagnosed, but GS cells were also positive for CD 56 and CD41. Although CD56 had not been examined initially, he might have been had myeloid/NK cell precursor acute leukemia and CD41 might be acquired later in the course of the disease. It is known that AML M0, M7 and myeloid/NK cell precursor acute leukemia have poor prognoses, nevertheless he survived for 6 years. It may be that intensive and repeated chemotherapy for AML can obtain excellent outcome in the elderly cases in good systemic condition and with favourable prognostic factors.

Aged↗
PubMed1990

Intradural granulocytic sarcoma presenting as a lumbar radiculopathy. Case report.

Granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, it can occur in isolation at various anatomical sites without hematological evidence of leukemia. The unique case of an elderly man presenting with right L2-3 radiculopathy is described. Intradural granulocytic sarcoma of the L-2 and L-3 nerve roots with extradural extension was found at surgery and he was treated with incomplete resection and antileukemic chemotherapy. Local recurrence at 3 months was treated with irradiation. Granulocytic sarcoma is frequently misdiagnosed and invariably progresses to acute leukemia. The chloroacetic acid esterase, granulocytic immunohistochemical markers, and electron microscopy appearance can aid in diagnosis. The prognosis is improved with initial aggressive antileukemic chemotherapy and local irradiation.

Aged↗
PubMed2002

Crystalline inclusions in granulocytic sarcoma.

Two cases of granulocytic sarcoma were found to contain numerous crystalline inclusions identified on hematoxylin-eosin-stained sections as clusters of pointed needlelike crystals present in foci of necrosis or within macrophages. The crystals were negative for chloroacetate esterase and myeloperoxidase. Electron microscopy demonstrated homogeneously dense, bipyramidal structures, indistinguishable from Charcot-Leyden crystals. Granulocytic sarcomas may contain crystalline inclusions similar to Charcot-Leyden crystals; these structures should be distinguished from crystalline immunoglobulin inclusions occurring in cases of plasma cell myeloma and lymphoplasmacytic lymphoma, which may have a similar appearance.

Bone Neoplasms↗
PubMed2002

Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma.

CONTEXT: Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. OBJECTIVES: To study the relationship between placental transmogrification and pulmonary hamartomas. DESIGN AND METHODS: Reports of 38 cases of pulmonary hamartomas during 18 years (1982-1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. RESULTS: Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%-90%) and Ki-67 (3%-5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit-positive cells were mast cells and not stem cells. CONCLUSIONS: Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.

Aged↗
PubMed1999

Morphologic, cytochemical staining, and ultrastructural characteristics of blood cells from eastern diamondback rattlesnakes (Crotalus adamanteus).

OBJECTIVE: To evaluate light microscopic, cytochemical, and ultrastructural characteristics of blood cells from eastern diamondback rattlesnakes. ANIMALS: 10 healthy snakes. PROCEDURE: Various stains, including Wright-Giemsa, benzidine peroxidase, Sudan black B, chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, leukocyte alkaline phosphatase, periodic acid-Schiff with diastase, and toluidine blue, were used to stain leukocytes differentially on multiple blood smears. Electron microscopy also was performed. RESULTS: Lymphocytes were the most commonly observed leukocyte and could be distinguished from thrombocytes, using periodic acid-Schiff stain with diastase. Azurophils also were commonly observed; their granules stained with peroxidase. Eosinophils were not identified; however, 2 morphologic variations of heterophils were seen in the blood of all snakes and were considered the same cell type at different stages of cytoplasmic granule development. Heterophil granules were better preserved, using a one-step Wright-Giemsa method that did not require alcohol fixation prior to staining. Degranulated heterophils were observed in all preparations. CONCLUSIONS: Most leukocytes of eastern diamondback rattlesnakes can be identified easily on Wright-Giemsa-stained preparations. However, hematologic stains that do not require alcohol fixing prior to staining may be preferred for leukocyte evaluation in certain reptiles. A limited degree of heterophil maturation may continue in the blood of healthy snakes. This, along with degranulation of heterophils, may result in a variable staining pattern in this cell type, regardless of the stain used. CLINICAL RELEVANCE: Results provide baseline data for use in hematologic testing in diagnosis of disease and monitoring of treatment of sick or injured snakes.

Animals↗
PubMed1999

Chronic granulocytic leukemia in a dog.

A 4-year-old spayed dog had a recent history of increased WBC count and surgery for pyometra. Two weeks after surgery, WBC count was 57,640 cells/microliter; neutrophilia and immature myelocytic cells were detected. Histologic examination of liver and lymph node biopsy specimens revealed active granulopoiesis. Immature granulocytes that stained with chloroacetate esterase were evident. Bone marrow was excessively cellular and contained numerous granulocytes and blast cells. A diagnosis of chronic granulocytic leukemia was made on the basis of test results. Treatment with hydroxyurea returned the WBC count to reference range within 2 months. Mean survival time for dogs with chronic granulocytic leukemia is approximately 1 year; the dog of this report has remained healthy for more than 2 years. Chronic granulocytic leukemia is a rare neoplastic disease that must be differentiated from leukemoid inflammatory reactions. Although commonly described as a diagnosis determined by exclusion, diagnosis of chronic granulocytic leukemia should be made on the basis of specific criteria.

Alopecia↗
PubMed1975

Thymus-independent antigens: the preparation of covalent, hapten-ficoll conjugates.

A general approach is presented for covalently attaching carboxyl and primary amino groups to Ficoll and other high molecular weight polysaccharides in a readily controlled manner. The polysaccharides are omicron-carboxymethylated with chloroacetate in NaOH solutions. Amino groups are next introduced by monoamide formation with ethylenediamine using a water-soluble carbodiimide. Reactions are carried out in aqueous solutions; excess reactants and by-products are removed by dialysis. Three different ways for coupling the 2,4-dinitrophenyl hapten to the amino derivative of Ficoll are described. Preliminary evidence indicates that 2,4-dinitrophenyl-Ficolls, prepared by procedures developed in this study, are potent thymus-independent antigens which can specifically stimulate B cells both in vivo and in vitro. Hapten-Ficoll conjugates should be exceptionally useful for studies of B lymphocyte activation because of the ready availability of the starting material and the ease with which a wide variety of hapten derivatives may be prepared.

Amino Sugars↗
PubMed2000

Adenosine and selective A(2A) receptor agonists reduce ischemia/reperfusion injury of rat liver mainly by inhibiting leukocyte activation.

To examine whether adenosine reduces ischemia/reperfusion (I/R)-induced liver injury by inhibiting leukocyte activation via A(2) receptor (A(2)R) stimulation, we investigated the effects of adenosine and selective A(2A) receptor (A(2A)R) agonists (YT-146 and CGS21680C) on I/R-induced liver injury in rats. Adenosine, YT-146, and CGS21680C, in the concentration of 10(-7) to 10(-5) M, significantly inhibited neutrophil elastase release by about 30 to 40% and increased intracellular Ca(2+) concentrations in isolated neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro. Adenosine, YT-146, and CGS21680C, in the concentration of 10(-7) to 10(-5) M, significantly inhibited tumor necrosis factor (TNF)-alpha production by monocytes stimulated with endotoxin by about 50%. Although ZM241385, a selective A(2A)R antagonist, significantly enhanced the increase in neutrophil elastase release and intracellular Ca(2+) concentrations in neutrophils stimulated with fMLP, this agent did not affect the endotoxin-induced TNF-alpha production by monocytes. Rats were subjected to liver ischemia for 60 min. Serum levels of transaminases increased after hepatic I/R, peaking at 12 h after reperfusion. The i.v. infusion of adenosine (1 and 10 mg/kg/h), YT-146 (0.1 and 1 mg/kg/h), and CGS21680C (0.1 and 1 mg/kg/h) significantly inhibited the I/R-induced increase in serum transaminase levels 12 h after reperfusion. The I/R-induced decrease in hepatic tissue blood flow was significantly prevented by adenosine and YT-146. Hepatic levels of TNF-alpha, cytokine-induced neutrophil chemoattractant (equivalent to human interleukin-8), and myeloperoxidase were significantly increased after I/R. These increases were significantly inhibited by the administration of adenosine, YT-146, and CGS21680C. Although the histological neutrophil accumulation in the liver was significantly increased after I/R as evaluated by the naphthol AS-D chloroacetate technique, the administration of adenosine, YT-146, and CGS21680C significantly inhibited this increase. These findings suggest that adenosine reduces I/R-induced liver injury both by inhibiting the synthesis of inflammatory mediators and by inhibiting neutrophil degranulation directly, probably through A(2A)R stimulation.

Adenosine↗