Colloidal synthesis of inorganic fullerene nanoparticles and hollow spheres of titanium disulfide.

The synthesis of inorganic fullerene (IF) nanoparticles and IF hollow spheres of titanium disulfide by a simple colloidal route is reported. The injection temperature of the titanium precursor into the solvent mixture was found to be important in controlling the morphology.

A K(ATP) channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias.

Low concentrations of certain K(ATP) channel openers have been reported to exert a moderate inhibitory effect on arrhythmias during post-ischaemic early myocardial reperfusion, but the accompanying effects on the time course of changes in action potentials in intact hearts have not yet been studied. We report that in rat isolated hearts, reperfusion following 10 min of regional no-flow ischaemia was associated with both an acute, marked, but transient, shortening of ventricular repolarisation (by 63%) during reperfusion, and a high incidence (90%) of ventricular tachyarrhythmias. The K(ATP) channel opener Ro 31-6930 [2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide], delivered prior to ischaemia at a relatively low concentration (0.

Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K+ (KATP) channels open during the first 10 min of regional ischaemia in Langendorff-perfused rat hearts. Changes in monophasic action potentials and arrhythmias were studied during myocardial ischaemia in both the presence and absence of pharmacological KATP modulation. Ligation of the left main coronary artery for 10 min did not shorten the action potential duration (APD).

Effect of sodium nitroprusside and L-arginine methyl ester on rat hearts stored at 4 degrees C for 24 h.

1. This study examined the effects of altering nitric oxide levels with sodium nitroprusside or L-arginine in rat hearts stored hypothermically.2.

Mast cell amines and inosineinduced vasoconstriction in the rat hind limb.

Under certain circumstances injected inosine causes a net vasoconstrictive effect on the arterioles, which has been attributed to 5-hydroxytryptamine (5HT) released in response to adenosine type 3 (A(3)) receptor stimulation of mast cells residing in the adventitia. We have sought further evidence for this hypothesis using blood vessels of the rat hind limb perfused in vitro at constant rate with a gelatin-containing physiological salt solution. Injection of inosine (2.

Some cyclic nucleotides reduce phenylephrine-induced and phorbol ester-induced constriction of the rat anterior mesenteric artery.

1. Vasoconstrictor responses to phenylephrine (PE) and to 12-deoxyphorbol 13-phenyl-acetate in the rat isolated perfused anterior mesenteric artery were inhibited by pretreating the artery with isoprenaline (ISOP), sodium nitroprusside or 8-bromoguanosine 3':5'-cyclic monophosphate, but not with 8-bromoadenosine 3':5'-cyclic monophosphate. 2.

Effect of protein kinase C inhibitors and 2,3-butanedione monoxime on the long-term hypothermic preservation of isolated rat hearts.

1. This study examines the protective effect of staurosporine, chelerythrine, Ro 31-8220 and 2,3-butanedione monoxime in rat hearts during hypothermic storage. 2.

Inhibition of NO-synthase and degranulation of rat omental mast cells in vitro.

Mast cell amines, platelet-activating factor (PAF), thromboxanes and leukotrienes have been shown to be released during nitric oxide-synthase inhibition in the rat intestine. Mast cells in rat isolated omentum (OMCs) or isolated from the rat peritoneal cavity (PMCs) have been used here to investigate the relationship(s) between these agents. N-nitro-L-arginine methyl ester (L-NAME, 100 muM) caused some degranulation of OMCs, but no enhancement of histamine release from PMCs.

Degranulation of rat omental mast cells by A(1) receptor agonists in vitro.

The haemodynamic effects of adenosine are thought to result in part from a release of mast cell amines via A3 receptor stimulation. To investigate the nature of the receptors involved in adenosine-induced mast cell degranulation in the rat isolated omentum we have used adenosine analogues with varying specificities as activators of the A(1), A(2) and A(3) receptors, and antagonists with differing specificities for A(1) and A(2) receptors. Analogues which act predominantly as A(1) (e.

Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro.

Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 muM) or indomethacin (1 muM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls.

Long-term preservation of the rat isolated heart with staurosporine and 2,3-butanedione monoxime.

The present study was designed to investigate the effectiveness of staurosporine and 2,3-butanedione monoxime (BDM) in preserving cardiac function of long-term hypothermic-stored hearts. Rat isolated hearts were perfused very slowly at 4 degrees C for 16 hr with a storage buffer solution containing staurosporine and BDM. Heart functions were then examined during 2 hr of normothermic reperfusion.

Rate of perfusion modulates colloidal carbon leakage from rat intestinal microvessels in vitro.

In order to investigate the effects of varying the rate of flow on endothelial integrity the rat isolated small intestinal vasculature was perfused at 1, 5, 10 or 20 ml/min with a gelatin-containing physiological salt solution (GPSS), followed by an injection of colloidal carbon suspension (CC). Significantly greater microvascular CC leakage occurred at 1 or 5 ml/min than at 10 or 20 ml/ mitt. CC leakage at the two slower rates of flow was reduced by adding red blood cells to the GPSS, suggesting that the microvascular endothelium became hypoxic when perfused with GPSS at 1 or 5 ml/min.

Possible bi-directional link between ET(A) receptors and protein kinase C in rat blood vessels.

Possible links have been investigated between activation of protein kinase C (PKC) and endothelin (ET) production by small blood vessels. Perfusion pressures were recorded from rat isolated mesenteric artery, with or without the small intestine attached, before and after addition to the perfusate of either ET-1, ET-3 or the PKC activator 12-deoxyphorbol 13-phenylacetate (DOPPA). Rises in perfusion pressure in response to ET-1 (10(-8) M)or DOPPA (10(-6) M) were reduced significantly by pre-treatment with either the ET(A) receptor antagonist PD151242 (10(-6) M) or the PKC inhibitor Ro 31-8220 (10(-6) M).

Vasoconstriction in rat isolated mesentery and small intestine in response to various activators of protein kinase C.

The vasculature of rat isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution (GPSS). When 5-hydroxytryptamine (5HT, 1 x 10(-4) M), or the calcium ionophore A23187 (1 x 10(-4) M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1 x 10(-6) M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1 x 10(-6) M) or thymeleatoxin (TMX, 1 x 10(-6) M) was added to the GPSS for 5 min there was a gradual rise in perfusion pressure, whereas resiniferatoxin (RFX, 1 x 10(-6) M) was without effect. Pre-treatment of the tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced the rise in perfusion pressure in response to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187.

Stimulation of protein kinase C activity may increase microvascular permeability to colloidal carbon via alpha-isoenzyme.

The vasculature of the isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution in vitro. Various phorbol-related compounds that are known to have different affinities for the protein kinase C (PKC) isoenzymes, and bradykinin (BK), were tested for their ability to cause the microvascular endothelium to become permeable to injected colloidal carbon (CC). Phorbol 12,13-dibutyrate (PDB), 12-deoxyphorbol 13-phenylacetate (DOPPA), thymeleatoxin (TMX), and resiniferatoxin (RFX), each at a concentration of 1 microM, were found to increase permeability.

Effect of pre-treating rat atria with potassium channel blocking drugs on the electrical and mechanical responses to phenylephrine.

Action potential duration (APD) and systolic developed tension (SDT) were recorded from electrically paced rat atria before, during and after treatment with phenylephrine in vitro. Phenylephrine caused a prolongation of APD and an increase in SDT, the magnitude of which depended upon the frequency of pacing of the atria. Effects very similar to those elicited by phenylephrine were produced by exposing the atria to 4-aminopyridine, 3,4-diaminopyridine, CsCl, amantadine or sparteine.

Lectin-induced increase in microvascular permeability to colloidal carbon in vitro may involve protein kinase C activation.

Two plant lectins, wheat germ agglutinin (WGA) and concanavalin A (Con A), which are known to bind to endothelial cells (ECs), were found to increase the leakage of colloidal carbon (CC) into the walls of microvessels in the villi of rat small intestine, when added to a gelatin-containing perfusate (GPSS) at a concentration of 10 micrograms/ml. Pretreatment of the microvessels with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced this effect. In contrast, the leakage of CC in response to A23187 (1 x 10(-4) M) was not affected by Ro 31-8220.

Competitive titration for probing low-abundance ion channel mRNA molecules in normal and regionally-ischaemic heart tissue.

We have measured the expression levels of a range of distinct ion channel genes in the apex/ventricle region and sino-atrial node (SAN) sub-regions of heart under conditions in which conventional Northern hybridization or ribonuclease protection methods were too insensitive or non-quantitative. The abundance of six potassium channel mRNAs was determined in relation to a single synthetic competitor RNA template which was co-reverse transcribed and PCR-amplified. By these methods we have shown that coronary artery ligation procedures which induce anoxia and ischaemic scarring in the apical region reduce amplifiable message abundance in a time-dependent, but non-specific manner.

Possible involvement of microtubules in platelet-activating factor-induced increases in microvascular permeability in vitro.

The blood vessels of the rat small intestine were perfused in vitro with a gelatin-containing physiological salt solution (GPSS). The addition of platelet-activating factor (PAF, 5 microM), podophyllotoxin (50 microM), colcemid (50 microM), or nocodazole (50 microM) to the GPSS for 5 min caused an increase in vascular permeability. This was manifested as an increased trapping of circulating colloidal carbon (CC) within the walls and was assessed using semiautomated image analysis.

Involvement of protein kinase C in the control of microvascular permeability to colloidal carbon.

The vasculature of the rat small intestine and attached mesentery was perfused in vitro with a gelatin-containing physiological salt solution (GPSS). The inclusion of colloidal carbon (CC) in the perfusate towards the end of the experimental period enabled the "leakiness" of microvessels in the villi to be determined, since "leaky" vessels trap CC in their walls. Addition to the perfusate of the inflammatory agonists platelet-activating factor (PAF, 5 x 10(-6) M) or 5-hydroxytryptamine (5-HT, 1 x 10(-4) M), or the microtubule-disrupting agents podophyllotoxin (5 x 10(-5) M), or colcemid (5 x 10(-5) M), or the protein kinase C (PKC) activator phorbol 12, 13-dibutyrate (PDB, 1 x 10(-6) M), caused significantly increased microvascular "blackening" as assessed by image analysis.

Phorbol 12,13-dibutyrate produces negative inotropism and selective antagonism of responses to adrenoceptor agonists in rat atria.

Rat atria loaded in vitro with the dye INDO-1 produced fluorescence signals indicative of changes in cytoplasmic calcium ion concentration ([Ca2+]c). Such atria showed systolic/diastolic fluctuations indicative of a systolic rise and a diastolic fall in both tension and [Ca2+]c. Positively inotropic responses of the atria to isoprenaline, phenylephrine, ouabain or 4-aminopyridine were associated with fluorescence changes indicative of increased systolic increments in [Ca2+]c.

Impact on survival of a decade of change in the management of patients who have sustained a myocardial infarction.

The survival of 906 consecutive patients who had sustained an acute myocardial infarction was monitored between the beginning of week 2 and the end of week 52. Deaths which occurred during this period were successfully predicted in terms of just 6 features; namely the value of left ventricular systolic time intervals measured during the 1st week, the occurrence of a myocardial infarction prior to the current hospitalisation, the patient's age, the coexistence of diabetes mellitus, the presence of left or right bundle branch blocks, and the administration of a diuretic agent while the patient was in hospital. By means of stepwise linear discriminant analysis predictions of mortality among the first 302 patients based upon these 6 features were 80% specific and 63% sensitive.

Antiarrhythmic and electrophysiological effects of amiodarone, lignocaine, and penticainide in anaesthetised rats.

Objective: The aim was to correlate the relative abilities of amiodarone, lignocaine, and penticainide in suppressing ventricular tachyarrhythmias in response to coronary artery occlusion with their relative abilities to prolong ventricular functional refractory periods and to reduce intraventricular conduction velocities in anaesthetised open chest rats.

Methods: Functional refractory period was measured with a paired electrical stimulation technique. Intraventricular conduction velocity was monitored using the QRS duration of the ECG.

Effects of 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB8) on rat atrial muscle.

Rat atria loaded in vitro with the dye INDO-1 produced fluorescence signals indicative of changes in cytoplasmic calcium ion concentration ([Ca2+]c). Such atria showed systolic/diastolic fluctuations in fluorescence indicative of a systolic rise and a diastolic fall in [Ca2+] while being superfused with a solution containing a normal Ca2+ concentration. Some atria were then exposed to a low [Ca2+] in the superfusate.

Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism.

Objective: We have previously reported that, in thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine.

Design And Patients: Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over-replaced, as defined by an elevated free T4 and a sub-normal TSH.