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PubMed1999

[Distribution of lymphocytes to tumor tissue and regional lymph nodes in patients with gastric cancer--the effects of oral administration of OK-432].

We attempted to clarify the accumulation of radiolabeled lymphocytes to tumors and regional lymph nodes in patients with gastric carcinoma. The effects of oral administration of OK-432 were also studied. Five patients with gastric cancer and one who underwent endoscopic mucosal resection, were entered in the study. Prior to the tracer study in 3 patients with gastric cancer, 5 KE of OK-432 was administered for 2 days. Peripheral mononuclear cells were separated and labeled with [111] In-tropolone. After the resection of stomach, tumor tissue, normal gastric mucosa, regional lymph nodes, and non-regional lymph nodes were dissected and radioactivity was measured by a gamma-counter. Accumulation of lymphocytes to the tumor tissue and n1 lymph node station was more than two times that in the normal gastric mucosa and ten times that in non-regional lymph nodes. Accumulation of lymphocytes to the n2 station was strongly enhanced by oral administration of OK-432.

Administration, Oral↗
PubMed1976

Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines.

The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284). The stimulant of central alpha-adrenoceptors, clonidine, suppressed PGO(1284) and PGO(PCPA) in very small doses. Apomorphine in high doses had inconsistent depressant effects which were probably not related to its stimulant action on DA receptors. Release of brain NA by dexamphetamine and beta-tetrahydronaphthylamine decreased the density of PGO waves, alpha-Methyldopa diminished PGO(PCPA) but not PGO(1284. The MAO-inhibitor, nialamide, depressed PGO(PCPA) more than PCO(1284), whereas pheniprazine was inactive. The inhibitor of catechol-O-methyltransferase, tropolone, reduced the density of bially blocks the uptake of NA, was more potent on PGO(PCPA) than on PGO(1284). The alpha-adrenoceptor blocking agent, phenosybenzamine, markedly increased the density of PGO(PCPA). Similar effects were obtained with thioridazine and clozapine, which aare also known to be blockers of central alpha-adrenoceptors. Inhibition of tyrosine hydroxylase (by alpha-methyltyrosine) and of DA-beta-hydroxylase (by disulfiram or Ro 8-1981), in addition to the inhibition of tryptophan hydroxylase by PCPA, induced PGO waves comparable in density and temporal distribution to those occurring following the application of Ro 4-1284. The acute bilateral lesion of the dorsal and caudal parts of thel ocus coeruleus increased the density of PGO(PCPA). The results strongly suggest that, in addition to the 5-hydroxytryptaminergic system, noradrenergic neurones, probably originating in the locus coeruleus, depress the neurones in the pontine reticular formation involved in the generation of PGO waves.

Animals↗
PubMed1992

A quantitative autoradiographic study of the heterogeneous activity distribution of different indium-111-labeled radiopharmaceuticals in rat tissues.

In light of the increased interest in small scale dosimetry, this paper presents a quantitative autoradiographic method for evaluation of heterogeneous activity distribution in tissues. This was studied in rat tissues after administration of 111In-chloride, -oxine, -tropolone, 111In-labeled homologous blood cells and 111In-anti-CEA-F(ab')2, using quantitative whole-body autoradiography. Quantification was performed utilizing an image analyzing system designed for whole-body autoradiographs. Very heterogeneous activity distribution was found in several tissues including the liver, spleen, kidneys, bone marrow, lymph nodes and testes. Notable was the high 111In uptake in organs characterized as rapidly proliferating, and known to have numerous transferrin receptors. In the gastrointestinal tract, all activity was associated with the intestinal walls. The heterogeneous tissue distribution shown in this investigation accentuates the necessity for performing detailed studies of the tissue distribution of radiopharmaceuticals. This is especially important for the radiation dosimetry of radionuclides emitting beta-particles or low energy electrons. We suggest whole-body autoradiography as an excellent implement to determine local activity concentrations in organs and tissues necessary for accurate absorbed dose calculations.

Animals↗
PubMed1992

Flavonoid potentiation of contractile responses in rat blood vessels.

Certain bioflavonoids and phenolic compounds have long been known to enhance catecholamine responses, in vivo and in vitro. In the present studies the flavone, baicalein, potentiated nerve-stimulated contractions in vitro in rat tail and femoral artery isometric ring preparations. Inhibition of catecholamine reuptake with cocaine or catecholamine metabolism with tropolone and parglyine (monoamine oxidase and catecholamine-O-methyl transferase inhibitors, respectively) did not alter baicalein's ability to potentiate contractile responses to nerve stimulation. Baicalein (10(-5) M), the prototype flavone, also increased sensitivity to exogenous norepinephrine, serotonin, arginine vasopressin and to the noncatecholamine alpha-1 and alpha-2 adrenergic agonists, cirazoline and tramazoline. Structure-function studies indicated that flavone potentiation required three contiguous A or B ring hydroxylations. Several nonflavone phenol derivatives with three contiguous hydroxyls also potentiated nerve stimulation responses. As baicalein is a potent lipoxygenase inhibitor, comparisons were made between potentiating ability and lipoxygenase inhibitory activity in a series of flavonoids. There was no direct correlation between inhibition of 12-hydroxy-5,8,10,14-eicosatetraenoic acid levels in thrombin stimulated human platelets and potentiation of contractile responses in the femoral artery. Additionally, the specific substrate analog lipoxygenase inhibitor, 5,8,11-eicosatriynoic acid, and the cyclooxygenase inhibitor, ibuprofen, were nonpotentiating. Ibuprofen pretreatment did not alter the potentiating action of baicalein. It is concluded that flavonoids with three contiguous hydroxyls on either the A or B ring increase in vitro vascular responsiveness via a post-synaptic process, independent of cyclooxygenase, lipoxygenase, monoamine oxidase or catecholamine-O-methyl transferase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMedDate not supplied

Quantitation of comparative thrombogenicity of dog, pig, and human platelets in a hemodialyzer.

Comparative platelet thrombogenicity was quantified with In111 labeled platelets. The platelets collected from the blood of Beagle dogs, Yorkshire pigs, and human volunteers were labeled with detergent free In111 tropolone, and sham hemodialysis (SHD) was performed with a hollow fiber dialyzer in a flow loop at 37 degrees C, with flow rates of 7, 150, and 270 ml/min. After SHD, hemodialyzer radioactivity was measured with an ionization chamber, gamma counter, and it was imaged with a gamma camera. The mean values of hemodialyzer-adherent platelet radioactivity were calculated. Canine platelets are more thrombogenic than porcine and human platelets. Quantitation of comparative thrombogenicity with In111 platelets may provide an estimation of prosthesis induced thrombogenicity of human platelets from animal studies.

Animals↗
PubMedDate not supplied

Cytotoxic activity of azulenequinones against human oral tumor cell lines.

We investigated twenty-seven azulenequinone derivatives for their relative cytotoxicity against three human normal cell lines (HGF, HPC, HPLF) and four human tumor cell lines (HSG, HSC-2, HSC-3, HL-60). Parent 1,5-azulenequinone showed potent and some tumor-specific cytotoxicity. Halogenated derivatives of 1,5- and 1,7-azulenequinone showed potent cytotoxicity, but lower tumor-specific cytotoxicity. In contrast to other azulenequinones, amino derivatives such as 3-amino-1,5- and 1, 7-azulenequinones showed relatively lower cytotoxic activity. The 3-Phenoxy-1,5-azuleneqinone derivative showed higher cytotoxicity than the 3-phenoxy-1, 7-azulenequinone derivative. 1,5- and 1,7-Azulenequinones generally showed higher cytotoxicity, as compared with tropolones and azulene derivatives. 3- (3-Guaiazulenyl)-1, 5-azulenequinone [12] and 7-isopropyl-3- (4-methylanilino)-2-methyl- 1, 5-azulenequinone [24] showed a relatively higher TS value and induced apoptosis (internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9) in HL-60 and HSC-2 cells, possibly via the activation of both mitochondria-independent (extrinsic) and -dependent (intrinsic) pathways. Western blot analysis showed that [24] slightly increased the intracellular concentration of pro-apoptotic proteins (Bad, Bax) in HSC-2 cells, whereas [12] was much less active. None of the twenty-seven azulenequinones showed anti-HIV activity. These results suggest [12] and [24] as possible candidates for future cancer chemotherapy.

Anti-HIV Agents↗
PubMed1992

The redistribution of lymphocytes during adrenaline infusion. An in vivo study with radiolabelled cells.

Adrenergic activation is known to occur in sepsis and after major surgery or trauma. An elevated serum concentration of adrenaline is followed by lymphocytosis in peripheral blood even in splenectomized patients. The purpose of the present study was to clarify the redistribution of lymphocytes in the tissues during adrenaline infusion. Lymphocytes were isolated from 24 rabbits, labelled with indium-111-tropolone and reinjected into the rabbits. The next day the rabbits were anaesthetized. Eight rabbits received 3 micrograms of adrenaline i.v. followed by 0.2 micrograms/min, eight received 300 micrograms of adrenaline i.v. followed by 20 micrograms/min, while eight received a saline infusion and served as a control group. The activity of labelled cells was imaged with a gamma camera and computer before, during and after adrenaline infusion. The activity of the spleen decreased to 90% and 94% of initial values during low and high doses of adrenaline. The activity of the bone marrow decreased to 91% and 96%, respectively, while the activity of the heart/lung and the liver increased to 107% and 106% with the high dose of adrenaline. In peripheral blood the lymphocytes increased 10%. It is concluded that lymphocytes are redistributed from spleen and bone marrow to peripheral blood, lungs and liver during adrenaline infusion in this animal model.

Animals↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor enhances exudation of neutrophils to sites of inflammatory challenge in vivo.

Priming of neutrophil oxidative responses by granulocyte-macrophage colony-stimulating factor (GM-CSF) has been well documented, but its inhibitory effect on chemotaxis has led to concerns that its therapeutic administration may compromise neutrophil emigration to sites of infection and inflammation. We developed a murine model to determine the biodistribution kinetics of [111In] labeled neutrophils and used this model to study the influence of recombinant GM-CSF on neutrophil influx into inflammatory sites. Murine neutrophils were harvested from the peritoneal exudate 3 h after the intraperitoneal injection of fluid thioglycollate medium, radiolabeled with [111In]tropolonate, and resuspended in 10% acid/citrate/dextrose: 90% Hanks' balanced salt solution (without Ca2+ and Mg2+) at pH 6.5 for re-injection. To assess the in vivo effect of GM-CSF, 22 mice were injected intravenously with labeled neutrophils 1 h prior to intraperitoneal challenge with thioglycollate or saline. Half of the mice also received 2.0 micrograms of recombinant murine GM-CSF intravenously at the time of injection of labeled cells. GM-CSF had no influence on the influx of labeled cells to the peritoneum of animals that received i.p. saline, but increased by nearly 50% the cellular migration elicited by i.p. injection of thioglycollate. We conclude that GM-CSF does not impair, but rather enhances, the ability of circulating neutrophils to respond to thioglycollate-induced inflammation in vivo. The model we describe provides a useful and controllable method to investigate the effects of GM-CSF and other cytokines on the biodistribution kinetics and emigration of neutrophils in vivo.

Animals↗
PubMed1990

Investigation by scintigraphic methods of platelet kinetics under normal and septic shock conditions in the experimental baboon model.

This study concerned the correlation of platelet kinetics with the pathogenic course of septic shock and adult respiratory distress syndrome (ARDS) in the anesthetised baboon model. 111In-tropolonate platelets were traced in vivo in normal baboons (n = 7) and in Escherichia coli-infected baboons, which were reinjected with the labeled autologous platelets either 2 hr after the onset of the E. coli infusion (procedure A: n = 4) or simultaneously with the infusion (procedure B; n = 3). One minute images were taken hourly for 5 hr, using a gamma camera and data processor. Time-activity curves were obtained for platelet clearance from the blood and the lungs and for platelet accumulation in the liver and spleen. A significant retention of platelets in the lungs of baboons with E. coli-induced septic shock was noted, as well as an accelerated clearance from the circulation. Platelets were distributed mainly to the spleen after induction of bacteremia, later substantially moved to the liver, and even later moved back to the spleen.

Animals↗
PubMed1990

Endotoxin testing with limulus amoebocyte lysate in a radiopharmaceutical containing chelated metallic radionuclides and chelating agents.

The gel formation by endotoxin with limulus amoebocyte lysate (LAL) solution requires the presence of free calcium ions. The chelating agents and radiopharmaceuticals prepared from the chelating agents always reduce the available free calcium levels present in the kits used for the testing of apyrogenicity and thus inhibit gel formation of LAL with E. Coli endotoxin (ET). This inhibition of gel formation could be reversed by the addition of excess free calcium ions or the excessive dilution of radiopharmaceuticals and chelating agents. The tests of positive control (0.2 ml ET units and LAL), inhibition control (0.1 ml sample, 0.1 ml ET and LAL), and negative control (0.1 ml sterile saline and LAL) were carried out with the fresh preparation (0.1 ml) of samples (triplicate), tropolone, ACD anticoagulant, and 99mTc-labeled radiopharmaceuticals. In the Ca-supplemented tests, 0.1 ml of 60 mM sterile calcium chloride solution was added to the test solutions and incubated for 60 min at 37 degrees centigrade. The results of gel formation (+ve and -ve) and normalization of inhibition control tests with Ca-supplement indicate that commercial LAL kits need extra calcium ions for the correct testing of the apyrogenicity of chelate-containing radiopharmaceuticals and chelating agents.

Limulus Test↗
PubMed1989

[Antiplatelet effects of combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia].

Antiplatelet effects of combination therapy with aspirin and ticlopidine were investigated in comparison with single aspirin or ticlopidine therapy in 62 patients with cerebral thrombosis or transient ischemic attack. The 14, 21 and 27 patients were given orally daily aspirin 300mg, ticlopidine 200mg and aspirin 81mg with ticlopidine 100mg, respectively. Various platelet function tests were performed before and a week after medication. They included platelet aggregation (PA) to adenosine diphosphate (ADP), arachidonic acid (AA) and platelet activating factor (PAF) with turbidimetry, plasma beta-thromboglobulin (beta TG), platelet factor 4(PF4), thromboxane B2(TXB2) and 6keto-prostaglandin-F1 alpha(6keto PGF1 alpha) with radioimmunoassay, bleeding time with Simplate device, and platelet survival and lysis with Indium-111-tropolone-labelled platelets. Aspirin inhibited PA to ADP and AA but not to PAF, while ticlopidine inhibited PA to ADP and PAF but not to AA. In contrast, aspirin with ticlopidine inhibited PA to all of these agonists despite their smaller doses used. Aspirin reduced plasma TXB2 but not beta TG or PF4, while ticlopidine reduced beta TG and PF4 but not TXB2. On the contrary, aspirin with ticlopidine reduced TXB2 as well as beta TG and PF4. 6keto PGF1 alpha tended to be reduced by aspirin 300mg alone but not by ticlopidine with or without aspirin 81mg. Bleeding time was significantly prolonged by aspirin or ticlopidine alone, although most prolongation was produced by combination of aspirin and ticlopidine. Platelet survival and lysis remained unaltered in 4 patients treated with aspirin or ticlopidine alone, whereas platelet survival was prolonged and platelet lysis was reduced in 4 patients treated with both aspirin and ticlopidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Technic and clinical use of radioactive labelling of autologous granulocytes].

Gamma-camera imaging after injection of radiolabelled autologous leucocytes can be very helpful in the diagnosis, localization and further clinical treatment of inflammatory diseases. We present a technique allowing sterile separation of white blood cells and labelling with 99mTc-phytate or -oxine and with 111In-oxine, -oxine sulphate or -tropolone. The method is non-invasive and the radiation dose amounts to less than 80 mrad using 100 microCi 111Indium. The use of radiolabelled granulocytes is of particular diagnostic value in patients with septicaemia of unknown origin. Whole body scanning allows not only visualization of enhanced splenic uptake in septicaemia, but also localization of an inflammatory process. Preferential indications for a diagnostic approach using radiolabelled granulocytes are inflammatory abdominal processes which cannot easily be documented by means of other non-invasive techniques, such as inflammatory bowel disease (Crohn's diseases and ulcerative colitis), arthritic processes and abscesses of the liver and spleen, as well as subphrenic and retroperitoneal abscesses. Untreated osteomyelitis can be located with the help of labelled granulocytes, but in patients treated with antibiotics a false negative result is obtained in approximately 50% of cases for as yet unknown reasons, even in the presence of a still active osteomyelitic process.

Abscess↗
PubMed1988

Monocyte retention and migration in pulmonary inflammation. Requirement for neutrophils.

The acute inflammatory process is characterized by an orderly progression of events; an initial phase of early neutrophil accumulation and a later phase of mononuclear cell (including monocyte) accumulation. The mechanisms which control the transition from one phase to the other are largely unknown. We present a rabbit model of C5 fragment (C5f)-induced lung inflammation in which purified radiolabeled peripheral blood neutrophils and monocytes were used as probes to monitor the retention and emigration of these leukocytes into well localized areas of inflammation. Neutrophil preparations (greater than 95% pure) were isolated by discontinuous plasma-Percoll density gradients, and monocyte preparations (greater than 91% pure) were isolated by counterflow cell elutriation, labeled with 111Indium-tropolonate, and intravenously infused into separate recipient animals. The monocytes circulated with a half-life of approximately 30 hours. The retention of labeled monocytes or neutrophils within the lung was monitored scintigraphically. C5f-induced monocyte lung retention was delayed 2 to 4 hours compared with neutrophil lung retention. Radiolabeled neutrophils were selectively retained in the area of C5f-induced inflammation (right cranial lung lobe, RCL) as early as 20 minutes after the induction of the inflammatory response, reached a maximum by 2 hours, and were not retained by 48 hours after C5f instillation. The signal inducing C5f-induced monocyte lung retention was shown to be transient. Monocytes were selectively retained in the RCL if the area of inflammation was induced 2 to 4 hours but not 15 minutes or 16 hours before their infusion. The time course of C5f-induced monocyte migration into the alveolar space determined by lavage analysis was delayed 2 to 3 hours compared with neutrophil migration. Neutrophils selectively migrated into the RCL 1 to 2 hours after the induction of the inflammatory response, reached a maximum by 4 hours, and had disappeared by 48 hours. Radiolabeled monocytes selectively migrated into the RCL 3 to 4 hours after the induction of the inflammatory response, reached a maximum by 4 hours, and remained present through 48 hours. The total number of labeled and unlabeled mononuclear cells present in the C5f-treated RCL lavage at 48 hours was significantly increased above controls. The signal for this monocyte migration (as for lung retention) was shown to be transient in that radiolabeled monocytes did not migrate when infused 16 hours after the induction of the inflammatory response. C5f did not induce monocyte lung retention nor monocyte migration into the alveolar space of animals rendered neutropenic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The role of detergent in labeling of Erysipelothrix rhusiopathiae bacteria.

The chelating agents oxine, acetylacetone, tropolone, and 2-mercaptopyridine 1-oxide were analysed for their suitability in labeling the bacterium Erysipelothrix rhusiopathiae (E.r.), strain B10, with 111In and 67Ga. The labeling conditions were improved. The bactericidal activity of the labeling process was investigated. The different chelates did not result in a significant difference in labeling yield. The addition of 0.01% detergent to the labeling buffer doubled the labeling yield up to 45%. Labeled bacteria were injected intravenously into rats. The percentage organ distribution was determined and compared with a control group.

Animals↗
PubMed1987

Human monocyte adherence: a primary effect of chemotactic factors on the monocyte to stimulate adherence to human endothelium.

Monocyte emigration into areas of inflammation is initiated by monocyte adherence to the microvascular endothelium which may be induced by the local production of chemotactic factors at the inflammatory site. However, it is not clear whether such stimuli act on the monocyte and/or the endothelial cell to promote this effect. Accordingly, the effect of the chemotactic peptides C5a des arg and formyl-methionyl-leucyl-phenylalanine (FMLP) on human monocyte adherence to human microvascular endothelial cell monolayers was investigated in vitro. Monocytes (92 to 98% pure) were isolated by discontinuous plasma-Percoll density gradients and cell elutriation, methods designed to minimize monocyte exposure to endotoxin. Mean spontaneous (unstimulated) adherence of 111Indium-tropolonate-radiolabeled monocytes to microvascular endothelial cell monolayers was 19.7% +/- 1.3. Monocyte adherence to microvascular endothelial cell monolayers was stimulated in a dose-response fashion in the presence of C5a des arg or FMLP to a maximum mean adherence of 47.2% +/- 2.9 or 43.8% +/- 2.2, respectively. C5a des arg or FMLP stimulated monocytes to adhere to monolayers of human vascular smooth muscle cells, human dermal fibroblasts, or serum-coated plastic wells in a comparable fashion as to endothelial cells. The simultaneous presence of both chemotactic peptides C5a des arg and FMLP in the assay system stimulated monocyte adherence to the same degree as either stimulus alone. This finding suggested that those monocytes stimulated to adhere by C5a des arg were the same subpopulation responding to FMLP. Spontaneous monocyte adherence (in the absence of chemotactic peptides) to both endothelial cell monolayers and serum-coated plastic wells was reduced in the presence of plasma, but chemotactic peptides induced a significant, albeit reduced, adhesion of monocytes in this circumstance. The pretreatment of monocytes with either C5a des arg or FMLP prior to the adherence assay induced stimulus-specific desensitization of monocyte adherence. Neither a desensitization nor stimulated monocyte adherence occurred when endothelial cell monolayers or serum-coated plastic wells were pretreated with either of the chemotactic peptides. The fixation of endothelial cell monolayers prior to the adherence assay did not alter the degree of spontaneous, C5a des arg-stimulated, or FMLP-stimulated monocyte adherence. These data suggest that the stimulated adhesion of monocytes to endothelial cells by C5a des arg or FMLP represents primarily an effect of these chemotactic peptides on the monocyte.

Cell Adhesion↗
PubMed1985

Simplified and efficient labeling of human platelets in plasma using indium-111-2-mercaptopyridine-N-oxide: preparation and evaluation.

The need for a gamma-emitting radioactive agent that will label platelets in plasma efficiently by a procedure that can be used uniformly in each laboratory is well recognized. A water soluble sodium salt of 2-Mercaptopyridine-N-oxide (Merc) was evaluated that quantitatively chelated 111ln at a pH range of 0.7 to 7.4, and allowed greater than 80% incorporation of 111ln in platelets in plasma. This was dependent on pH, Merc concentration, and platelet concentration. Platelets were labeled using either preformed [111ln]Merc or incubating platelets with 2.5 micrograms dry Merc first and then with 111ln. The latter method provided a simple kit procedure that labeled platelets with negligible alteration of in vitro aggregability. In dogs, labeled platelets had normal survival (7.5 days), 66 +/- 6.6% recovery, detected vascular thrombi (thrombi/blood = 59.4), and pulmonary emboli (PE/blood = 46.2) by scintigraphy. In the kit procedure, the use of Merc compared favorably to that of oxine and tropolone.

Animals↗
PubMed1974

Contact allergy from Frullania and respiratory allergy from Thuja.

Occupational allergic contact dermatitis in 52 forest-workers was caused by sesquiterpene lactones from liverworts (Frullania) and by usnic acid from lichens which grow on various trees including cedar (Thuja). Occupational asthma and rhinitis in 35 wood-workers was caused by wood dust of western red cedar (Thuja plicata). Characteristically, the respiratory symptoms occurred in the evening and at night and not during working hours; inhalation challenge with plicatic acid from the wood provoked immediate, late or dual (combined immediate and late) asthmatic reactions. Another class of compounds, tropolones, derived from Thuja plicata wood, was responsible for dermatitis in a wood-worker. These distinct industrial hazards in two groups of workers at the tree-felling and wood-working levels in the forest-products industry can be identified by clinical history and examination supplemented by specific cutaneous or respiratory clinical investigation.

Alcohols↗
PubMed1971

Mechanism of potentiation of contractor responses to catecholamines by methylxanthines in aortic strips.

1. Caffeine and theophylline increased the amplitude of contractor esponses of untreated and reserpine pretreated rabbit aortic strips to catecholamines (adrenaline, alpha-methylnoradrenaline, noradrenaline). Responses to amines without both the 3- and 4-OH groups in the benzene ring (methoxamine, phenylephrine, Synephrine) were not increased by theophylline and only those to Synephrine were slightly enhanced by caffeine.2. Compounds which inhibit catechol-O-methyltransferase (pyrogallol, tropolone, U-0521) potentiated responses to catecholamines and abolished the enhancing effect of theophylline and caffeine. Also, the potentiation produced by inhibitors of O-methylation was significantly reduced in the presence of the methylxanthines.3. Experiments done with the aid of the technique of oil immersion, to eliminate the diffusion of drug from the tissue into the bathing medium, showed that theophylline and caffeine decreased the rate of inactivation of adrenaline by O-methylation.4. These findings indicate that methylxanthines potentiate the contractor responses to catecholamines in aortic strips by inhibiting their extraneuronal inactivation.

Animals↗