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1.
Sci Total Environ ; 667: 160-165, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-30826677

ABSTRACT

Monitoring of the coastline and coastal processes, in particular sediment movement, is vital to ensure that erosion response is appropriate given the dynamic nature of coastal systems. This should take place regularly over long periods and it is important that data are collected from submerged portions of the littoral zone, as well as the visible beach. This highlights two limitations in existing coastal monitoring techniques: 1. they require largely manual operation and 2. are limited to the visible beach, which results in an incomplete picture of what is happening in the coastal zone. Due to the current difficulties in gathering data beneath the sea surface, this paper reviews wireless sensor network (WSN) technology as a means to overcome these limitations. Analysis showed that WSNs are a promising technology for coastal monitoring, not only in terms of overcoming limitations, but also in terms of cost, safety, and the size of areas they are able to monitor. Previous work using WSNs in this environment is somewhat limited, especially as most current methods are largely limited to the visible beach, and do not consider submerged areas of the coastal zone. From consideration of the physical environment, geological and geographical processes, and informed by advances in technology, research gaps are identified, discussed and evaluated to provide strategies for implementation of WSNs to monitor sediment transport.

3.
Mech Dev ; 100(2): 205-15, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11165478

ABSTRACT

We report the characterization of a gene trap integration that provides an in situ marker for one of the earliest events in liver development. Expression of the reporter gene is observed at the nine-somite stage in the hepatic field of the foregut endoderm. At 10.5 days post-coitus expression is observed exclusively and at high levels in the majority of cells in the developing liver bud. As development proceeds the proportion of expressing cells decreases with expression in adult liver being restricted to a few sporadic cells. This therefore provides the earliest, most specific in situ marker of the hepatic lineage reported to date and will be useful in the further characterization of the inductive events involved in hepatic specification. Molecular characterization of the gene trap insertion suggests that the expression pattern is the result of alternative promoter use in the ankyrin repeat-containing gene, gtar.


Subject(s)
Digestive System/embryology , Endoderm/physiology , Liver/embryology , Protein Biosynthesis , Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Cell Lineage , Cloning, Molecular , Crosses, Genetic , DNA, Complementary/metabolism , DNA-Binding Proteins , Embryo, Mammalian/metabolism , Female , Genetic Markers , In Situ Hybridization, Fluorescence , Male , Mice , Mice, Inbred C57BL , Models, Genetic , Molecular Sequence Data , Phenotype , Promoter Regions, Genetic , Protein Isoforms , Proteins/chemistry , RNA, Messenger/metabolism , RNA-Binding Proteins , Reverse Transcriptase Polymerase Chain Reaction , Ribonucleases/metabolism , Stem Cells/metabolism , Time Factors
4.
Crit Rev Eukaryot Gene Expr ; 11(4): 279-97, 2001.
Article in English | MEDLINE | ID: mdl-12067068

ABSTRACT

The functional role of the osteoblast nuclear matrix has been a matter of supposition. Its presumed function as an architectural agent of transcription derives primarily from the low solubility of nuclear matrix proteins and their typical localization into discrete subnuclear domains. In addressing how the nuclear matrix regulates skeletal genes, the authors compare Nmp4, Cbfal, and YY1 for the purpose of profiling osteoblast nuclear matrix transcription factors. All three proteins contribute to the transcription of ECM genes and partition into the osteoblast nuclear matrix via a nuclear matrix targeting domain. The authors propose that osteoblast nuclear matrix transcription factors involved in ECM regulation generally have the capacity to alter DNA geometry and reciprocally respond to DNA as an allosteric ligand. This may allow these proteins to adapt to the local nuclear architecture and generate the pattern of regulation specified by that architecture via unmasking of the appropriate transactivation domains. Osteoblast nuclear matrix transcription factors may also act as transcriptional adaptor molecules by supporting the formation of higher order protein complexes along target gene promoters. The genes encoding all three proteins considered here have trinucleotide repeat domains, although the significance of this is unclear. There is no canonical nuclear matrix binding motif, but finger-like structures may be suited for anchoring proteins to discrete subnuclear domains. Finally, the ability to leave the osteoblast nuclear matrix may be as important to the function of some nuclear matrix transcription factors as their association with this subcompartment.


Subject(s)
Bone and Bones/physiology , DNA-Binding Proteins/genetics , Gene Expression Regulation , Nuclear Matrix-Associated Proteins , Nuclear Matrix/physiology , Nuclear Proteins/genetics , Trans-Activators/genetics , Transcription Factors/genetics , Animals , Antigens, Nuclear , Base Sequence , Consensus Sequence , Erythroid-Specific DNA-Binding Factors , Humans , Mice , Molecular Sequence Data , Protein Isoforms/genetics , Rats , YY1 Transcription Factor
5.
Clin Radiol ; 55(8): 622-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10964734

ABSTRACT

AIM: To assess the accuracy of the absent bow tie sign in diagnosing bucket handle meniscal tears (BHT) of the knee menisci. MATERIALS AND METHODS: During a 3-year period, we correlated the MRI and arthroscopic findings and the presence of the various signs. One hundred and seven knees were reviewed: 74 where either MRI or arthroscopy had identified a BHT and 33 which were either normal (31), or a simple tear was identified (2). All cases were reviewed by a single radiologist with a musculoskeletal interest blinded to the original results. Each was assessed for the presence of (1) a central meniscal fragment, (2) the double posterior cruciate ligament (PCL) sign, (3) the bow tie sign and (4) the contribution of a 3D-volume sequence. RESULTS: Optimal results were obtained using standard sequences and a 3D-volume sequence, giving a sensitivity of 74% and positive predictive value of 89%. The bow tie sign gave a sensitivity of 71% and positive predictive value of 76%, significantly less than previous reports. The 18 BHTs diagnosed by arthroscopy but missed by MRI showed other abnormal findings at MRI and were not reported as normal. CONCLUSION: We were not able to reproduce the previously reported high sensitivity and specificity of the absent bow tie sign. Despite optimization of all factors, the accurate diagnosis of a bucket handle tear remains difficult, and is most reliably made by identifying a central meniscal fragment, rather than relying on secondary signs such as the absent bow tie sign.


Subject(s)
Magnetic Resonance Imaging/methods , Tibial Meniscus Injuries , Arthroscopy/methods , Diagnosis, Differential , Humans , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
6.
Neuron ; 26(3): 659-70, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10896161

ABSTRACT

AMPA and NMDA receptors are coexpressed at many central synapses, but the factors that control the ratio of these two receptors are not well understood. We recorded mixed miniature or evoked synaptic currents arising from coactivation of AMPA and NMDA receptors and found that long-lasting changes in activity scaled both currents up and down proportionally through changes in the number of postsynaptic receptors. The ratio of NMDA to AMPA current was similar at different synapses onto the same neuron, and this relationship was preserved following activity-dependent synaptic scaling. These data show that AMPA and NMDA receptors are tightly coregulated by activity at synapses at which they are both expressed and suggest that a mechanism exists to actively maintain a constant receptor ratio across a neuron's synapses.


Subject(s)
Neocortex/physiology , Receptors, AMPA/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Synapses/physiology , Animals , Artifacts , Cells, Cultured , Electric Conductivity , Excitatory Postsynaptic Potentials/physiology , Glutamic Acid/pharmacology , Neocortex/cytology , Nerve Endings/drug effects , Nerve Endings/physiology , Neurons/physiology , Rats
7.
J Vasc Interv Radiol ; 11(2 Pt 1): 225-31, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10716395

ABSTRACT

PURPOSE: To compare the technical success and immediate and long-term outcomes of tunneled central venous catheters placed in comparative cohorts via the subclavian vein (SCV) and the internal jugular vein (IJV) routes. MATERIALS AND METHODS: This was a prospective observational single-center study of consecutive procedures. Between November 1993 and June 1995, 99 catheters were placed via the SCV and between December 1997 and July 1998, 109 catheters were placed via the IJV. Procedural data were recorded in both cohorts by completion of a proforma by the primary operator. RESULTS: Follow-up data were available in 96% of the SCV and 87% of the IJV cohorts. The average procedure time was significantly shorter in the IJV group and technical success was 100% versus 97% in the SCV group, but this did not reach statistical significance. The procedure-related pneumothorax rate and the rate of symptomatic venous thrombosis were significantly lower in the IJV cohort (P = .023, P = .015). Fewer catheters were removed prematurely due to sepsis in the IJV group (P = .043). CONCLUSIONS: The IJV route is associated with comparable technical success, and lower major procedural complication and venous thrombosis rates, with fewer catheters removed prematurely. The right IJV approach with ultrasound guidance is recommended as the route of choice for the placement of tunneled central venous catheters.


Subject(s)
Catheterization, Central Venous , Jugular Veins , Subclavian Vein , Catheterization, Central Venous/instrumentation , Catheterization, Central Venous/methods , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Time Factors
8.
Clin Radiol ; 54(11): 778-80, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10580773

ABSTRACT

Multiple Symmetric Lipomatosis (MSL) is a rare disorder of lipid metabolism which is mainly seen in Mediterranean and eastern European populations, which results in massive fat accumulation mainly around the neck and back. The main differential diagnosis lies between MSL and the fat accumulation of Cushing's disease, and liposarcoma. This case demonstrates that MR imaging is a valuable aid to the diagnosis and treatment of this disease by giving excellent definition of soft tissue and vascular structures, allowing accurate assessment and preoperative planning of the disease.


Subject(s)
Lipomatosis, Multiple Symmetrical/diagnosis , Magnetic Resonance Imaging , Adult , Humans , Male
10.
J Med Genet ; 31(2): 108-14, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8182714

ABSTRACT

Over three decades, 12 cases of mosaicism for an autosomal rearrangement were recognised in the major cytogenetics laboratories in New Zealand, eight of which were studied between 1990 and 1992. One case inferentially involved the gonad, eight the soma, and three both gonad and soma. This mosaicism could have arisen as a postzygotic event either in a conceptus that was initially normal, with the generation of an abnormal cell line, or in a conceptus having a supernumerary chromosome which was lost at a subsequent mitosis, thereby restoring a normal cell line. Three of the 12 cases involved a presumed direct duplication, an otherwise very uncommon rearrangement. This may indicate a propensity for direct duplications to arise at mitosis rather than at meiosis; unequal sister chromatid exchange is a plausible mechanism. Mosaicism has clinical relevance for genetic counselling, as an intragonadal cell line carrying a rearrangement could generate multiple unbalanced gametes. Mosaicism for an autosomal rearrangement my be very much more common that is, or ever could be, recognised.


Subject(s)
Chromosome Aberrations/genetics , Chromosomes, Human/ultrastructure , Mosaicism/genetics , Adolescent , Adult , Child , Child, Preschool , Chromosome Disorders , Female , Humans , Infant, Newborn , Male
11.
Lett Appl Microbiol ; 18(2): 97-99, 1994 Feb.
Article in English | MEDLINE | ID: mdl-34892920

ABSTRACT

A comparative study was made of the ability of three commercial identification kits to confirm the identity of motile aeromonads isolated from foods. The kits included the API 20E, API 20NE and Microbact 24E. The results showed that both the API 20NE and Microbact 24E correctly identified 97.5% of isolates but the API 20E only 72.5%.

13.
Ann Genet ; 35(3): 161-3, 1992.
Article in English | MEDLINE | ID: mdl-1466565

ABSTRACT

A neonate with aniridia was found to have a one band paracentric inversion of the short arm of chromosome 4. This was initially difficult to interpret on high resolution banding. The inversion was present in three generations of the family.


Subject(s)
Aniridia/genetics , Chromosome Inversion , Chromosomes, Human, Pair 4 , Glaucoma/congenital , Family , Glaucoma/genetics , Humans , Infant, Newborn , Karyotyping , Male
14.
Br J Pharmacol ; 104(1): 263-9, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1664764

ABSTRACT

1. The ability of cromakalim to modulate several different types of neuroeffector transmission has been assessed in guinea-pig isolated trachea. 2. In trachea treated with propranolol (10(-6) M) and indomethacin (2.8 x 10(-6) M), stimulation of the extrinsic vagal nerves evoked contractions which were blocked by hexamethonium (5 x 10(-4) M) or by tetrodotoxin (TTX; 10(-6) M). Cromakalim (10(-5) M) caused a two fold rightward shift of the frequency-response curve. 3. In carinal trachea treated with propranolol and indomethacin, transmural stimulation evoked an initial, rapid contraction followed by a more sustained secondary contraction. The initial, rapid contractile response was virtually ablated by atropine (10(-6) M) or by TTX but was resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) caused a concentration-dependent rightward shift of the frequency-response curve for the initial contraction. 4. In carinal trachea treated with atropine, propranolol and indomethacin, transmural stimulation evoked only the secondary (non-adrenergic, non-cholinergic (NANC] contractile responses. These were markedly reduced by TTX but were resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) suppressed the NANC contractile responses in a concentration-dependent manner. This action could be offset by glibenclamide (10(-6) M). 5. In trachea treated with atropine, histamine (10(-4) M), propranolol and indomethacin, transmural stimulation evoked NANC relaxant responses. Cromakalim (up to 10(-5) M) was without effect on the frequency-response curve for the stimulation of NANC inhibitory nerves. 6. Tested on trachea bathed by drug-free Krebs solution, cromakalim (10(-7)-10(-5) M) caused concentration-dependent suppression of tracheal tone. In trachea treated with propranolol and indomethacin, cromakalim (10- 7-1O- 5 M) caused concentration-dependent antagonism of acetylcholine (ACh). In trachea treated with atropine, propranolol and indomethacin, cromakalim (up to 10- 5M) failed to antagonize effects of either histamine or substance P.7. It is concluded that cromakalim can inhibit cholinergic (excitatory) neuroeffector transmission in the trachea but only at a concentration having demonstrable inhibitory activity against the action of exogenous ACh and the spontaneous tone of the airways smooth muscle. In contrast, cromakalim may depress NANC excitatory (putative peptidergic) neuroeffector transmission at a concentration below that exerting inhibitory activity on airways smooth muscle. Cromakalim does not concurrently depress NANC inhibitory neuroeffector transmission. Depression of NANC excitatory neuroeffector transmission could explain the ability of cromakalim to suppress airway hyperreactivity or bronchial asthma at doses lacking direct relaxant effect on airways smooth muscle.


Subject(s)
Benzopyrans/pharmacology , Bronchodilator Agents/pharmacology , Muscle, Smooth/drug effects , Pyrroles/pharmacology , Animals , Autonomic Nervous System/physiology , Cromakalim , Electric Stimulation , Female , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/innervation , Muscle, Smooth/physiology , Neuromuscular Junction/drug effects , Neurons/drug effects , Parasympathetic Nervous System/physiology , Synaptic Transmission/drug effects , Trachea/drug effects , Trachea/innervation , Trachea/physiology , Vagus Nerve/drug effects , Vagus Nerve/physiology
15.
Aust N Z J Obstet Gynaecol ; 31(3): 246-8, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1804088

ABSTRACT

Trisomy 7, in mosaic state, was identified at chorionic villus sampling. The pregnancy was closely followed, and proceeded uneventfully. Mosaic trisomy 7 was confirmed in the term placenta, the organ having no structural abnormalities; the karyotype of the phenotypically normal baby was 46,XY. Trisomy 7, mosaic or nonmosaic, detected at chorionic villus sampling in an ultrasonographically normal pregnancy, appears typically to be associated with a normal fetal karyotype, and placental growth, structure, and function are not discernibly compromised.


Subject(s)
Chromosomes, Human, Pair 7 , Placenta , Trisomy , Adult , Chorionic Villi Sampling , Female , Humans , Infant, Newborn , Male , Phenotype , Placenta/pathology , Pregnancy
16.
Eur J Pharmacol ; 192(3): 417-26, 1991 Jan 17.
Article in English | MEDLINE | ID: mdl-1647318

ABSTRACT

In Triton X-100-skinned trachealis muscle, neither papaverine nor AH 21-132 modified responses to Ca2+. The (-)-enantiomer of AH 21-132 was more potent than the (+)-enantiomer both in relaxing intact trachealis muscle and in inhibiting tracheal cAMP phosphodiesterase (PDE). AH 21-132 (0.6 microM) potentiated forskolin in causing tracheal relaxation but did not potentiate isoprenaline, cromakalim or sodium nitrate. AH 21-132 (2 microM) potentiated all four agents in relaxing the trachea. AH 21-132 (1 microM) potentiated forskolin in increasing tissue cAMP content and, in higher concentration, itself increased tissue cAMP. Electrical effects of AH 21-132 included suppression of spontaneous slow waves and cellular hyperpolarisation. It is concluded that AH 21-132 lacks a direct depressant effect on the intracellular contractile machinery. The weight of evidence suggests that AH 21-132-induced relaxation results from inhibition of cAMP-PDE. However, in common with other PDE inhibitors. AH 21-132 increases tissue cAMP content only at concentration greater than that required to cause full relaxation.


Subject(s)
Airway Resistance/drug effects , Naphthyridines/pharmacology , Trachea/drug effects , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors , Action Potentials/drug effects , Animals , Benzopyrans/pharmacology , Biomechanical Phenomena , Cell Membrane/physiology , Colforsin/pharmacology , Cromakalim , Female , Guinea Pigs , In Vitro Techniques , Isoproterenol/pharmacology , Male , Nucleotides, Cyclic/metabolism , Papaverine/pharmacology , Pyrroles/pharmacology , Sodium Nitrite/pharmacology , Stereoisomerism
17.
N Z Med J ; 103(887): 157-8, 1990 Apr 11.
Article in English | MEDLINE | ID: mdl-2342673

ABSTRACT

We describe a series of 100 cases of prenatal genetic diagnosis using the technique of chorion villus sampling. The advantage of chorion villus sampling in terms of earlier diagnosis, and its disadvantage of a higher incidence of false results, compared with amniocentesis, are noted. The comparative risks for pregnancy loss are discussed.


Subject(s)
Chorionic Villi Sampling , Congenital Abnormalities/diagnosis , Abortion, Spontaneous/etiology , Chorionic Villi Sampling/adverse effects , False Negative Reactions , Female , Humans , New Zealand , Pregnancy , Pregnancy Trimester, First , Risk Factors
18.
N Z Med J ; 103(885): 101-2, 1990 Mar 14.
Article in English | MEDLINE | ID: mdl-1969132

ABSTRACT

We describe the use of techniques of DNA analysis for the diagnosis of certain inherited diseases during life and in the prenatal period, and for the diagnosis of some infectious diseases. Most local and some national needs for predictive genetic testing have been met. The costs of establishing our service are presented and are compared with those of similar services recently established in the United Kingdom. In the 12 month period described, running costs were approximately $57,000 and salaries for the two scientific officers and the medical technologist required to run the service were $97,000. The prerequisites for the successful running of such a service are discussed.


Subject(s)
DNA/analysis , Diagnostic Services/organization & administration , Costs and Cost Analysis , Diagnostic Services/economics , Diagnostic Services/statistics & numerical data , Diagnostic Services/trends , Evaluation Studies as Topic , Humans , Muscular Dystrophies/diagnosis , New Zealand , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
19.
Br J Pharmacol ; 97(4): 1165-73, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2551442

ABSTRACT

1. Experiments have been performed with the dual intent of analysing the mechanism by which AH 21-132 relaxes airways smooth muscle and determining whether the effects of this compound can be distinguished from those of theophylline. 2. AH 21-132 (0.25-8 microM) and theophylline (1-1000 microM) each caused concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachealis. The maximal effect of AH 21-132 was equivalent to that of theophylline. No evidence was obtained that the tissue became sensitized or desensitized to the action of AH 21-132. 3. Propranolol (1 microM) profoundly antagonized the tracheal relaxant action of isoprenaline but not that of AH 21-132. 4. In indomethacin (2.8 microM)-treated tissues, tone was induced by K+-rich (120 mM) Krebs solution, acetylcholine (ACh, 1 mM) or histamine (200 microM). Log concentration-relaxation curves for AH 21-132, isoprenaline and theophylline were all moved to the right in the presence of the spasmogens, the smallest rightward shift being induced by histamine and the greatest by ACh. While maximal effects of AH 21-132 and theophylline were unaffected by the spasmogens, that of isoprenaline was reduced by KCl and ACh. 5. In tissues treated with indomethacin (2.8 microM), AH 21-132 (0.1-100 microM) inhibited the spasmogenic effects of potassium chloride (KCl), ACh and histamine in a concentration-dependent manner. The inhibition was characterized by rightward shifts in the spasmogen concentration-effect curves with depression of their maxima. 6. In tissues treated with both indomethacin (2.8 microM) and ACh (1 mM), the removal of tracheal epithelium caused a small but significant leftward shift in the log concentration-relaxation curve for AH 21-132 but did not alter that for theophylline. 7. In tissues treated with indomethacin (2.8 microM) and maintained at 12 degrees C, theophylline (0.1-3.2 mM) caused concentration-dependent spasm. This effect was not shared by AH 21-132. 8. AH 21-132 (0.1-1000 microM) more potently inhibited the activity of cyclic AMP-dependent than of cyclic GMP-dependent phosphodiesterase derived from homogenates of guinea-pig trachealis. Theophylline, too, inhibited these enzymes but was less potent in each case than AH 21-132 and did not exhibit selectivity for the cyclic AMP-dependent enzyme. 9. It is concluded that AH 21-132 exerts a non-specific (i.e. effective no matter what agent is used to support tone) relaxant effect on the trachealis muscle which does not involve the activation of beta l-adrenoceptors. The profile of the relaxant action of AH 21-132 more closely resembles that of theophylline than that of isoprenaline. However, AH 21-132 can be differentiated from theophylline in that: (a) its relaxant potency is increased by epithelial removal; (b) it does not cause tracheal spasm; (c) it exhibits selectivity as an inhibitor of cyclic AMP-dependent as opposed to cyclic GMP-dependent phosphodiesterase. It is possible that the relaxant effects of AH 21-132 are related to its ability to inhibit cyclic nucleotide phosphodiesterases.


Subject(s)
Muscle, Smooth/drug effects , Naphthyridines/pharmacology , Phosphodiesterase Inhibitors/pharmacology , 2',3'-Cyclic-Nucleotide Phosphodiesterases/antagonists & inhibitors , Acetylcholine/pharmacology , Animals , Female , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Isoproterenol/pharmacology , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle Tonus/drug effects , Potassium/pharmacology , Theophylline/pharmacology , Trachea/drug effects , Xanthines/pharmacology
20.
Br J Pharmacol ; 97(4): 1174-81, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2551443

ABSTRACT

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle. The effective concentration ranges were 0.1-1OOO microM and 1-1000 microM, respectively. Theophylline, too, inhibited these enzymes but in each case was less potent than AH 21-132. 8. It is concluded that AH 21-132 is devoid of antagonist activity at adenosine Al receptors which modulate ACh release from intramural cholinergic nerves in the ileum. At concentrations greater than IO microM, AH 21-132 has a relaxant effect on intestinal smooth muscle characterized by suppression of spontaneous action potentials but by minor change in resting membrane potential. AH 21-132 previously has been reported to depress the spontaneous tone of trachealis muscle with an EC50 value of less than lO microM and the present experiments therefore show that this agent is much less potent in inhibiting intestinal muscle. This potency difference cannot be attributed to a tissuerelated difference in the potency of AH 21-132 as an inhibitor of cyclic AMP- or cyclic GMPdependent phosphodiesterases.


Subject(s)
Muscle, Smooth/drug effects , Naphthyridines/pharmacology , Phosphodiesterase Inhibitors/pharmacology , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors , Animals , Cecum/drug effects , Electric Stimulation , Electrophysiology , Female , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Male , Muscle Relaxation/drug effects , Potassium Chloride/pharmacology , Receptors, Purinergic/drug effects , Theophylline/pharmacology
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