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M M Teixeira

Publications and source records attributed to M M Teixeira.

At least 109 records · Page 6Linked to original sources
PubMed1995

Characterization of eosinophil homotypic aggregation.

Guinea pig peritoneal eosinophils stimulated by platelet-activating factor (PAF), leukotriene B4 (LTB4), and human recombinant C5a (C5a) undergo a rapid concentration-dependent and partially reversible homotypic aggregation as assessed by changes in light transmission. The phorbol ester phorbol myristate acetate similarly induces a concentration-dependent aggregation, which is, however, slower in onset, takes longer to reach maximal aggregation, and is irreversible. In addition, we confirmed, using light microscopy, that these agonist-induced changes in light transmission do indeed represent true homotypic aggregation. We further characterized the aggregation response and showed that there is homologous but little heterologous desensitization when PAF and LTB4 are used as stimuli. A requirement for both Ca2+ and Mg2+ for full manifestation of agonist-induced aggregation was observed. LTB4- and PAF-induced superoxide anion generation is enhanced by the diacyglycerol kinase inhibitor R59022, whereas aggregation induced by LTB4, but not PAF, is augmented. Lastly, we show that eosinophil aggregation is partially dependent on the adhesion glycoprotein CD18. In summary, therefore, we believe that eosinophil aggregation provides a useful and reliable measure of eosinophil activation.

Animals↗
PubMed1995

Mechanisms and pharmacological manipulation of eosinophil accumulation in vivo.

The presence of eosinophils and their products in tissues is frequently associated with the pathogenesis of allergic inflammation. A better understanding of how these cells are recruited from the microcirculation will help in the development of therapies targeted at allergic disorders. Here, Mauro Teixeira, Timothy Williams and Paul Hellewell describe the current concepts of eosinophil accumulation, examine the potential ways of modulating this process, and discuss whether antagonists of eosinophil-specific mediators or functional antagonists would be the preferred therapies.

Antibodies, Monoclonal↗
PubMed1995

Induction of leucocyte recruitment and bronchial hyperresponsiveness in the guinea pig by aerosol administration of interleukin-2.

Exposure of guinea pigs to an aerosol of human recombinant interleukin-2 (IL-2; 30 micrograms) resulted in an increase in the numbers of eosinophils and macrophages recovered from bronchoalveolar lavage fluid (BALF) 24 h later. This was accompanied by a bronchial hyperresponsiveness to intravenous acetylcholine. In guinea pigs sensitized to ovalbumin, exposure to IL-2 caused an increase in the number of macrophages, but not eosinophils in BALF and bronchial hyperresponsiveness to acetylcholine did not develop. In guinea pig skin, intradermal injection of IL-2 (10(-14) to 10(-9) mol/site) had no effect on 111In-eosinophil accumulation, measured over 3 h, suggesting that IL-2 does not act directly to recruit eosinophils. The hypothesis that IL-2 may be acting via release of interleukin-5 (IL-5) was tested using an antibody to IL-5 (TRFK-5; 1 mg/kg). Treatment with TRFK-5 1 h before exposure to IL-2 aerosol had no effect on the numbers of macrophages or eosinophils recovered from BALF 24 h later, although there was a tendency for reduced bronchial hyperresponsiveness to acetylcholine. These results suggest that (1) IL-2 is not a directly acting chemoattractant for eosinophils in the guinea pig, (2) the action of IL-2 to increase bronchial hyperresponsiveness is also indirect, partly via generation of IL-5, and (3) immunological sensitization alters the response of both eosinophils and bronchial smooth muscle to IL-2.

Administration, Inhalation↗
PubMed1994

Detection of trypanosomatid Phytomonas parasitic in plants by polymerase chain reaction amplification of small subunit ribosomal DNA.

To improve the diagnosis of Phytomonas infections in plants, we developed a polymerase chain reaction (PCR) assay using synthetic oligonucleotides complementary to conserved sequences of the 18S small subunit ribosomal (SSU) gene. From 10 ng upward of DNA of cultures of Phytomonas isolated from plants, fruits, and insects, PCR amplified an 800-bp DNA band that, after restriction analysis and probe hybridization, proved to be of 18S rDNA Phytomonas origin. PCR was also done with sap samples of tomatoes experimentally infected with Phytomonas, yielding amplified 800-bp ribosomal DNA bands before any flagellate could be detected by microscopic examination of the fruit sap.

Animals↗
PubMed1994

Effects of phosphodiesterase isoenzyme inhibitors on cutaneous inflammation in the guinea-pig.

1. Inflammation is central to the pathophysiology of asthma. The recent findings that different inflammatory cells may express different phosphodiesterase (PDE) isoenzymes have centered attention on inhibitors of these isoenzymes as new drugs for the treatment of asthma. In this study, we investigated the effect of different PDE isoenzyme inhibitors on the accumulation of 111In-labelled eosinophils and local oedema formation at sites of allergic- and mediator-induced inflammation in guinea-pig skin. 2. Systemic treatment with SK&F 94120, a type III PDE inhibitor, or zaprinast, a type V PDE inhibitor, had no effect on the 111In-eosinophil accumulation and oedema formation induced by i.d. injection of zymosan-activated plasma (ZAP), PAF, histamine or in a passive cutaneous anaphylaxis (PCA) reaction. 3. Systemic treatment with rolipram, a type IV PDE inhibitor, effectively inhibited 111In-eosinophil accumulation induced by ZAP, PAF, histamine and in a PCA reaction. However, oedema formation measured in the same sites was not affected. Systemic administration of higher doses of theophylline produced similar results. In contrast, 111In-neutrophil accumulation induced by ZAP or in a PCA reaction was not altered by systemic treatment with rolipram. 4. Locally-injected rolipram had little effect on 111In-eosinophil accumulation and oedema formation induced by histamine, PAF and in a PCA reaction. 5. These data show that systemic, but not local, treatment with rolipram effectively inhibits allergic- and mediator-induced 111In-eosinophil accumulation but not oedema formation or 111In-neutrophil accumulation. This, taken together with the potent inhibitory effects of PDE type IV inhibitors on eosinophil function in vitro, suggest that this class of drugs may be beneficial in disease states such as asthma where eosinophils are thought to play a major pathophysiological role.

Animals↗
PubMed1994

Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea-pig skin.

1. Intradermal injection of the complement fragment C5a des Arg induces local oedema formation that, in rabbits and man, is dependent on circulating neutrophils. Monoclonal antibodies to the leukocyte adhesion molecule CD11/CD18 block neutrophil accumulation and prevent neutrophil-dependent oedema formation. The role of CD11/CD18 in mediating eosinophil accumulation in vivo is less established. In this study we have used an anti-human CD18 monoclonal antibody, 6.5E, to investigate the neutrophil-dependency of oedema formation induced by C5a des Arg in guinea-pig skin. We also studied the role of CD18 in mediating eosinophil accumulation in the same model. 2. Stimulated adhesion of 111In-labelled guinea-pig neutrophils and eosinophils to serum-coated plastic was inhibited in a dose-dependent manner by 6.5E suggesting that the monoclonal antibody recognizes and blocks the guinea-pig CD18 adhesion molecule. 3. The accumulation of 111In-labelled neutrophils induced by zymosan-activated plasma (ZAP, as a source of C5a des Arg) in skin sites was reduced by up to 89% in animals treated intravenously with F(ab')2 fragments of 6.5E. ZAP-induced accumulation of 111In-labelled eosinophils was also greatly reduced (by up to 78%) by treatment with 6.5E. 4. Despite the inhibition of ZAP-induced neutrophil accumulation by 6.5E, local oedema formation in the same skin sites was unaffected, except at the top dose of ZAP, by treatment with the anti-CD18 monoclonal antibody, suggesting that the oedema response was largely neutrophil-independent. Indeed, ZAP-induced oedema formation was reduced by up to 81% by the H1 receptor antagonist, mepyramine. 5. Accumulation of 111 In-labelled eosinophils in a passive cutaneous anaphylactic (PCA) reaction was also blocked by treatment with 6.5E, while oedema formation in the same skin sites was unaffected.Intradermal injection of cationic protein-containing extracts of Schistosoma mansoni larvae also induced the accumulation of 111 In-labelled neutrophils and eosinophils which was abrogated by intravenous 6.5E.In contrast, extract-induced local oedema formation was similar in control and 6.5E-treated guinea-pigs.6. In summary, the local accumulation of radiolabelled neutrophils at sites of inflammation in guinea pigskin was dependent on the adhesion molecule CD18 while, in contrast, there was no evidence for neutrophil-dependent oedema formation in this species. Accumulation of radiolabelled eosinophils was also dependent on CD18.

Animals↗
PubMed1994

Effect of a 5-lipoxygenase inhibitor, ZM 230487, on cutaneous allergic inflammation in the guinea-pig.

1. Leukotrienes have potent biological effects in vitro and in vivo and are found in tissue and in biological fluids in various pathological conditions including allergic diseases. Leukotriene B4 (LTB4) is a potent stimulus for eosinophil accumulation and activation and there is much interest in determining its importance in mediating the accumulation of eosinophils at sites of allergic inflammation in vivo. In this study, we investigated the effects of a potent 5-lipoxygenase inhibitor, ZM 230487, on the accumulation of eosinophils and on local oedema formation in cutaneous inflammation in the guinea-pig. 2. The i.d. injection of increasing concentrations of arachidonic acid (AA) led to a dose-dependent accumulation of 111In-eosinophils but oedema formation was only significant at the top dose of AA tested (3 x 10(-8) mol per site). Co-injection of ZM 230487 with AA inhibited 111In-eosinophil accumulation up to 99% but the small oedema response to AA was only partially inhibited. AA-induced oedema formation was only effectively inhibited when a combination of a PAF antagonist, an antihistamine and ZM 230487 was used. 3. Local administration of the cyclo-oxygenase inhibitor, ibuprofen, partially inhibited AA-induced oedema formation suggesting that vasodilator prostaglandins may be released following i.d. injection of AA. AA-induced 111In-eosinophil accumulation was also partially inhibited by ibuprofen. 4. PAF-induced 111In-eosinophil accumulation was partially suppressed by local administration of ZM 230487. In contrast, LTB4-induced 111In-eosinophil accumulation was enhanced by ZM 230487. These data suggest that locally-released leukotrienes may modulate mediator-induced eosinophil accumulation. ZM 230487 had no effect on PAF- or LTB4-induced oedema formation. 5. ZM230487 significantly inhibited the accumulation of 111 In-eosinophils, but did not affect local oedema formation, in a passive cutaneous anaphylaxis (PCA) reaction. However, the PAF antagonist WEB 2086 either alone or in combination with ZM 230487 had no effect on "'In-eosinophil accumulation or oedema formation in the PCA reaction.6. In conclusion, it appears that a product of 5-lipoxygenase, probably LTB4, is important for the accumulation of "'In-eosinophils, but not local oedema formation, in the PCA reaction in guinea-pigskin. These data support a major role for LTB4 in allergic inflammation in the guinea-pig and make this animal (and the PCA model) suitable for studying the effects of inhibitors of leukotriene synthesis or action in vivo.

Animals↗
PubMed1994

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea-pig skin: contribution of neutrophils and endogenous mediators.

1. Mediators of inflammation can increase vascular permeability in at least two different ways: by acting directly on endothelial cells or, indirectly, through an incompletely understood mechanism, dependent on circulating neutrophils. Neutrophil-dependent oedema formation has been described in the skin of rabbits, rats, hamsters, mice and man. In contrast, we presented evidence in a previous study that local oedema formation induced by i.d. injection of chemoattractants in guinea-pig skin was neutrophil-independent. In the present study, we sought evidence of neutrophil-dependent oedema formation in immune-complex-mediated vasculitis, the reversed passive Arthus (RPA) reaction, in guinea-pig skin. We also investigated whether haemorrhage in the RPA reaction was neutrophil-dependent (as it is in other species) and the role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in contributing to the local inflammatory response. 2. In the RPA reaction, most oedema formation occurred over the first 60 min whereas 111In-neutrophil accumulation was still increasing from 60 to 240 min. The different kinetics of these two events suggested that they may be dissociated. 3. Oedema formation was partially inhibited by a long-acting PAF antagonist (UK-74,505) and an H1 histamine receptor antagonist (mepyramine) but not by a 5-lipoxygenase inhibitor (ZM 230487). A nitric oxide synthesis inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) suppressed oedema formation by 68% whereas a cyclo-oxygenase inhibitor suppressed oedema by 27%. 4. 111In-neutrophil accumulation in the RPA reaction was partially suppressed by UK-74,505. In contrast, ZM 230487 was without effect at doses which abrogated arachidonic acid-induced 111In-neutrophil accumulation. 5. The anti-CD18 monoclonal antibody, (mAb) 6.5E F(ab')2, effectively inhibited 111In-neutrophil accumulation induced by PAF, zymosan-activated plasma (ZAP) and in the RPA reaction. However, oedema formation measured in the same sites was not altered. In contrast, oedema formation in the RPA reaction was partially suppressed by 6.5E whole mAb which was 2.5 times more potent than 6.5EF(ab')2 at inhibiting guinea-pig neutrophil adhesion to protein-coated plastic. Haemorrhage induced by PAF and in the RPA reaction was significantly inhibited by 6.5E F(ab')2 pretreatment.6. We conclude that in the RPA reaction in guinea-pig skin, oedema formation is partially neutrophil dependent as assessed by using an anti-CD18 mAb, whereas ZAP-induced oedema formation is neutrophil-independent. Haemorrhage was also dependent on neutrophil accumulation. In addition, our studies support a role for PAF in mediating both oedema formation and "'In-neutrophil accumulation in the RPA reaction. Endogenous release of histamine also appears to be important in mediating oedema formation suggesting that mast cells play a critical role in increases of vascular permeability in inflammatory reactions in guinea-pig skin. Moreover, our results confirm previous findings which suggest a dominant role for nitric oxide in maintaining cutaneous blood flow in the guinea-pig.

Animals↗
PubMed1993

Mechanisms of the inflammatory response induced by extracts of Schistosoma mansoni larvae in guinea pig skin.

Penetration of skin by cercariae of Schistosoma mansoni is associated with a local inflammatory response characterised by leukocyte accumulation and tissue swelling. The significance of the inflammation and its relevance to infection of the host is unknown. In this study, we have investigated the mechanisms of the local inflammatory response induced by injecting extracts of Schistosoma mansoni cercariae into guinea pig skin. Intradermal injection of cercarial homogenate or cercarial transformation fluid induced a dose-dependent increase in local edema formation and accumulation of intravenously injected 111In-labeled eosinophils and neutrophils. The responses were rapid in onset and independent of new protein synthesis. The capacity of extracts to induce edema formation and leukocyte accumulation correlated significantly with their proteolytic activity. In addition, extract-induced inflammation was reduced by co-injection with Trasylol, soybean trypsin inhibitor, PMSF, or heparin. A combination of PMSF and heparin virtually abolished extract-induced inflammation. The known inhibitory effect of Trasylol on kallikrein prompted an investigation into the role of kinins in inducing local edema formation. The bradykinin antagonist HOE 140 substantially reduced extract-induced edema whereas bradykinin itself was weak at inducing leukocyte accumulation. The cyclooxygenase inhibitor ibuprofen, the platelet-activating factor antagonist WEB 2086, and the 5-lipoxygenase inhibitor PF5901 had no effect on edema formation. In contrast, extract-induced eosinophil accumulation was reduced by WEB 2086 and PF5901, suggesting that endogenous PAF and leukotriene B4 were involved in recruiting these cells to inflammatory sites. Thus, cercarial proteases induce a local inflammatory response in guinea pig skin that can be attributed, in part, to known mediators of inflammation. It remains to be established whether the response is protective for the host or whether it is beneficial for the parasite. Further understanding of the underlying mechanisms may provide a target for the pharmacologic control of infection in schistosomiasis.

Animals↗
PubMed1993

E-type prostaglandins enhance local oedema formation and neutrophil accumulation but suppress eosinophil accumulation in guinea-pig skin.

1. Prostaglandins possess both pro- and anti-inflammatory actions depending on their route of administration and the experimental model used. In this study, we have investigated the effect of locally injected prostaglandins on oedema formation, neutrophil accumulation and eosinophil accumulation in inflammatory responses in guinea-pig skin. 2. Prostaglandin E1 (PGE1) significantly enhanced local oedema formation induced by zymosan-activated plasma (ZAP), bradykinin and in a passive cutaneous anaphylactic (PCA) reaction. The accumulation of ZAP-induced 111In-labelled neutrophils was also significantly enhanced by PGE1. In addition, the prostacyclin analogue, iloprost, enhanced ZAP-induced responses. 3. In contrast PGE1 decreased the accumulation of 111In-labelled eosinophils in skin sites. This was demonstrated on eosinophil accumulation and local oedema formation induced by PAF, compound 48/80 and in the PCA reaction. PGE2 also suppressed eosinophil accumulation while iloprost had no detectable effect. 4. Isoprenaline inhibited eosinophil accumulation in a dose-dependent manner with no effect on local oedema formation, except in the case of responses to ZAP where suppression was observed. 5. The vasodilator neuropeptide, calcitonin gene-related peptide (CGRP), enhanced local oedema formation but had no detectable effect on eosinophil accumulation. 6. In conclusion, the magnitude of a given response to an inflammatory mediator in vivo depends on the net effect of stimulation of several cell types e.g. arteriolar smooth muscle cells, microvascular endothelial cells, mast cells and accumulating leukocytes. In this study, we have demonstrated that different components of the inflammatory response in guinea-pig skin can be differentially modulated by E-type prostaglandins and isoprenaline, suggesting that cyclic AMP has an important regulatory role.

Alprostadil↗
PubMed1993

Suppression by intradermal administration of heparin of eosinophil accumulation but not oedema formation in inflammatory reactions in guinea-pig skin.

1. Heparin is widely used in the treatment of thrombotic disorders and as an aid in surgery. Anti-inflammatory effects of heparin have also been described. In this study, we have investigated the effects of locally-injected heparin on the oedema formation and eosinophil accumulation induced by various inflammatory stimuli in guinea-pig skin. 2. Heparin dose-dependently suppressed the accumulation of 111In-labelled eosinophils induced by i.d. injection of zymosan-activated plasma (ZAP). The 111In-eosinophil accumulation induced by other inflammatory stimuli (compound 48/80, platelet activating factor, interleukin-8 and in a passive cutaneous anaphylaxis reaction) was also suppressed by locally-injected heparin. 3. Oedema formation in response to these same stimuli was not altered by the local injection of heparin. 4. Fucoidin, a negatively-charged sulphated algal polymer, had no effect on the 111In-eosinophil accumulation or oedema formation induced by ZAP. Nevertheless, fucoidin significantly suppressed the oedema formation induced by i.d. injection of cationic protein-containing extracts of Schistosoma mansoni larvae. Heparin also inhibited oedema induced by the extracts, suggesting that both fucoidin and heparin were effectively neutralizing the cationic protein of the extracts to inhibit their oedema-inducing activity. 5. Thus, heparin significantly inhibited the accumulation of 111In-eosinophils, but not oedema formation, induced by various inflammatory stimuli. This, taken together with the lack of effect of fucoidin, suggests that heparin interferes with the process of eosinophil trafficking by a mechanism that does not depend on neutralisation of the charge of the stimulatory molecules.

Administration, Cutaneous↗
PubMed1993

Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea-pig skin.

1. Oedema formation in skin is dependent on a synergism between mediators that increase vascular permeability and mediators that enhance local blood flow. Leukocyte accumulation is also enhanced by mediators that increase local blood flow. In this study, we have investigated whether nitric oxide (NO), an important endogenous vasodilator, could modulate oedema formation and leukocyte accumulation in guinea-pig skin. 2. Local administration of the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), dose-dependently inhibited the oedema formation induced in response to intrademal injection of bradykinin or histamine. L-NAME, but not NG-nitro-D-arginine methyl ester (D-NAME); also inhibited oedema formation in response to i.d. injection of platelet-activating factor (PAF), zymosan-activated plasma (ZAP) and in a passive cutaneous anaphylactic (PCA) reaction. 3. N-iminoethyl-L-ornithine (L-NIO) was less effective and about 100 times less potent than L-NAME in inhibiting bradykinin-induced oedema formation. The cyclo-oxygenase inhibitor, ibuprofen, had little effect on oedema responses induced by bradykinin, PAF and in a PCA reaction. On the other hand, histamine-induced oedema formation was significantly suppressed by ibuprofen. 4. The inhibition by L-NAME of bradykinin-induced oedema formation was reversed by co-injection of sodium nitroprusside (SNP) or prostaglandin E1 (PGE1). 5. L-NAME inhibited 111In-eosinophil and 111In-neutrophil accumulation induced by i.d. injection of ZAP. 111In-eosinophil accumulation induced by PAF and in the PCA reaction was also inhibited by L-NAME but not by D-NAME. 6. Co-injection of SNP or PGE1, reversed the inhibition by L-NAME of ZAP-induced oedema formation and 111In-neutrophil accumulation. SNP, but not PGE1, also reversed the effects of L-NAME on ZAP-induced 111In-eosinophil accumulation.7. L-NAME caused a significant decrease in basal cutaneous blood flow when injected alone or with bradykinin. Again, SNP or PGE, reversed the effects of L-NAME suggesting that the inhibitory action of L-NAME on oedema formation and cell accumulation was due to an inhibition of vasodilator tone in the microcirculation.8. Thus, it appears that in guinea-pig skin the inhibition of the production of endogenous NO inhibits both leukocyte accumulation and oedema formation induced by different mediators of inflammation.Since administration of L-NAME also causes a local decrease in basal blood flow, we suggest that this is the mechanism by which it exerts anti-inflammatory effects in this model.

Acute Disease↗
PubMed1992

Ribosomal DNA restriction analysis and synthetic oligonucleotide probing in the identification of genera of lower trypanosomatids.

Fifty-four species or isolates of insect trypanosomatids were examined for the presence of selected restriction enzyme sites in the small (SSU) and large (LSU) rRNA coding units of ribosomal genes. In the SSU, sites for Eco RI, Bgl II, Pst I, and Hind III were found to occur at the same location for all species examined, thus displaying a universal distribution among trypanosomatids. In the LSU, a site for Bgl II in the 24S-alpha sequence and sites for Hind III and Pst I in the 24S-beta sequence were found in all species examined. In contrast, a site for Pvu II in the SSU exhibited a genus-related distribution, being present in Crithidia and Herpetomonas but absent in Phytomonas. A site for Hind III in the 24S-alpha sequence of the LSU also exhibited genus-restricted distribution. The site was present in Crithidia but absent in Phytomonas and Herpetomonas. These findings were confirmed by dot hybridization with a synthetic oligonucleotide complementary to the 18S rRNA sequence containing the Pvu II site. Results point to the usefulness of restriction markers as diagnostic tools for distinguishing the lower trypanosomatid genera Crithidia, Herpetomonas, and Phytomonas at the same time revealing a marked complexity within the genus Leptomonas.

Amidohydrolases↗
PubMed1986

Stage-specific surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi identified by monoclonal antibodies.

Stage-specific Trypanosoma cruzi surface antigens were characterized by using monoclonal antibodies (MAb) which bind specifically to the metacyclic trypomastigotes derived from either the insect vector or acellular cultures. A protein with an apparent molecular weight of 90,000 was detected by the MAb 5E7 on the surface of cultured metacyclics of four strains of T. cruzi: G, CL, Y and Tulahuen. The MAb 1G7, which binds to an epitope of the 90 kDa antigen distinct from that recognized by the MAb 5E7, reacted with metacyclics of the G and Tulahuen strains but not of the Y or CL strain. A polypeptide of approximately 82 kDa, identified by the MAb 3F6, was found in the metacyclics of all four T. cruzi strains. The MAb 3F6 also detected a 75 kDa antigen in the G strain metacyclics. The stage-specific MAb and the polyclonal antibodies from mice protected against acute T. cruzi infection by immunization with killed G metacyclics identified the same set of major surface proteins of G metacyclic trypomastigotes.

Animals↗
PubMed1985

Radiological impact assessment of an abandoned radium salts factory.

A radiological assessment has been in progress, since 1978, on the environmental implications of an abandoned radium salts factory, operating in Portugal from 1912 to 1944. Some aspects of the study performed at the site are briefly described. They include the analysis of radium-226 concentrations in water and foodstuff and the identification of critical pathways. The resulting dose equivalents due to radium intake and external irradiation are evaluated for the two most exposed groups of the population, and compared with values from other regions. Their sensitivity to some of the factors assumed is also discussed.

Adult↗
PubMedDate not supplied

Murine chemokine CXCL2/KC is a surrogate marker for angiogenic activity in the inflammatory granulation tissue.

OBJECTIVES: A wide range of compounds inhibit formation of new blood vessels in a variety of models, accompanied by decreases in pro-angiogenic cytokines. The authors sought a surrogate marker for the complex process of neovascularization by correlating inhibition of cytokine production with anti-angiogenic effect. METHODS: Three anti-angiogenic compounds, clotrimazole (120 mg kg(-1) day(-1)), thalidomide (100 mg kg(-1) day(-1)), and rosiglitazone (10 mg kg(-1) day(-1)), were used to inhibit angiogenesis developing over 9 days, in sponges implanted subcutaneously in Swiss mice. Angiogenesis was assessed by hemoglobin content and by histology. Content of cytokines in implants was measured by specific immunoassays and accumulation of neutrophils or macrophages in implants by measuring myeloperoxidase or N-acetylglucosaminidase activity, respectively. RESULTS: These compounds caused equal inhibition of angiogenesis (about 40%). However, implant levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-alpha) or the macrophage chemoattractant cytokine, CCL2/MCP-1/JE, and accumulation of macrophages were more variably inhibited. Only the neutrophil chemokine, CXCL2/KC, was inhibited equally by the three compounds, in this model. CONCLUSIONS: Anti-angiogenic effect was most clearly and closely correlated with levels of the chemokine KC. Thus, measurement of the chemokine KC might provide an adequate surrogate marker for the functional process of neovascularization in our model.

Angiogenesis Inhibitors↗
PubMedDate not supplied

kDNA and rDNA sequences reveal a phylogenetic cluster of species originally placed in different genera of trypanosomatids.

Hybridization using kDNA and rDNA sequences as probes was performed to study phylogenetic relatedness of different species of trypanosomatids. Using this approach, we identified five organisms which had been classified as Phytomonas and Herpetomonas that were more closely correlated to each other phylogenetically than to any other species or isolates from either genera. These findings raise doubts about the validity of the current classification of Trypanosomatidae. Finally, we demonstrated the usefulness of kDNA sequences as an alternative to genomic sequences in obtaining phylogenetic information on trypanosomatids.

Animals↗