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Biomedical subjects

C Forster

Publications and source records attributed to C Forster.

At least 73 records · Page 4Linked to original sources
PubMed1995

Peripheral vascular smooth muscle responsiveness to tumour-promoting phorbol esters in pacing-induced heart failure.

Contractions of the dorsal pedal artery and saphenous vein to phorbol 12,13-dibutyrate (PDBu), 12-O-tetradecanoylphorbol 13-acetate (TPA), and 4 alpha-phorbol 12,13-didecanoate (4 alpha-phorbol) were measured from dogs with and without pacing-induced heart failure. The effects of polymyxin B (a relatively selective protein kinase C inhibitor), nifedipine (calcium channel blocker), and prazosin (alpha 1-adrenoceptor antagonist) were examined on the contractions developed to PDBu before heart failure, after 1 week of pacing, and at end-stage heart failure. PDBu and TPA, but not 4 alpha-phorbol, produced concentration-dependent increases in contractile force in both the artery and the vein. In the dorsal pedal artery, efficacy of and sensitivity to PDBu and TPA were enhanced after 1 week of pacing, but returned to control level at end-stage heart failure. In the saphenous vein, the concentration-effect curve to PDBu was displaced to the left after 1 week of pacing; EC50 values for PDBu were 3.2 x 10(-9) and 3.2 x 10(-8) M for 1 week paced and control, respectively. Polymyxin B significantly decreased the efficacy of PDBu in the dorsal pedal artery at all time points, but was less effective with advancing heart failure. In contrast, in the vein, there was a significant increase in inhibitory potential at end-stage heart failure. In all cases, nifedipine inhibited PDBu in a concentration-dependent manner. With the progression of heart failure, the contractions of the saphenous vein, developed to PDBu, became more sensitive to inhibition by nifedipine. Prazosin failed to inhibit vascular effects of PDBu. These results are discussed in terms of protein kinase C involvement in vascular contractions and its role in the pathogenesis of heart failure.

Animals↗
PubMed1995

Novel classes of responsive and unresponsive C nociceptors in human skin.

One hundred ninety-four cutaneous C-fibers were recorded from the human peroneal nerve; 118 units were found by mechanical stimuli and 76 units were detected by electrical stimulation through a surface electrode. Needle electrodes were then inserted for electrical intradermal stimulation in the innervation territory of the units. Afferent and efferent sympathetic C-fibers were identified by slowing of conduction velocity after activation either by physical or chemical skin stimuli, or by arousal maneuvers eliciting sympathetic reflexes. In addition to mechano-heat-responsive C units (CMH) also found in previous studies, we here report on novel classes of C nociceptors in human skin, namely, units responding only to mechanical stimuli (CM), units responding only to heating (CH), and units that were insensitive to mechanical and heating stimuli and also to sympathetic provocation tests (CMiHi). With the electrical search technique we found 45% CMH, 13% CM, 6% CH, 24% CMiHi, and 12% sympathetic units. Excitation by topically applied mustard oil occurred in 58% of CMH units, and in one-third of CM and CMiHi units, respectively. Some CM, CH, and CMiHi units were sensitized to heating and/or to mechanical stimuli after topical application of mustard oil or capsaicin. These units then acquired responsiveness to a stimulus modality to which they previously were insensitive. Such recruitment of previously silent nociceptors implies spatial summation to the nociceptive barrage at central levels, and may contribute both to primary hyperalgesia to heat and pressure after chemical irritation, and to secondary hyperalgesia as a consequence of central sensitization.

Adult↗
PubMed1994

Structure of the Pisum sativum seed lipoxygenase gene lox1:Ps:3.

We have isolated the Pisum sativum (pea) lox1:Ps:3 gene which encodes a lipoxygenase that is 84% identical in coding sequence to the LOX-3 gene from Glycine max (soybean). The 10028 bp sequence includes 5895 bp 5' to the transcription start site and 707 bp 3' to the stop codon. The coding region of lox1:Ps:3 contains eight introns, at positions equivalent to those in the soybean LOX-3 and L-4, the Phaseolus vulgaris (Frenchbean) LOX1, and the Pisum sativum lox1:Ps:2 genes. The first intron is unusually small. The 5'-flanking sequence contains two regions that have the potential to form hairpin structures, but few motifs known to interact with transcription factors. Despite their similarity in terms of expression, the lox1:Ps:3 and lox1:Ps:2 genes have little similarity within their 5'-flanking regions.

Genes, Plant↗
PubMed1994

Isolation of a pea (Pisum sativum) seed lipoxygenase promoter by inverse polymerase chain reaction and characterization of its expression in transgenic tobacco.

Part of the 5'-flanking sequence of a pea (Pisum sativum) lipoxygenase (LOX) gene was cloned, after amplification from genomic DNA by inverse polymerase chain reaction. Translational and transcriptional fusions of 818 bp of the 5'-flanking region and its deletion derivatives (-513 and -356) were made to a beta-glucuronidase (GUS)-coding sequence and introduced into tobacco. Analysis of T1 transformants showed that the 818 bp 5'-flanking sequence drove GUS expression in seeds that was temporally regulated in a fashion similar to the accumulation of LOX mRNA in developing pea seeds. Contrary to expectations, however, expression of the 818 bp promoter-GUS fusion was not seed-specific; GUS activity was highest in leaves and also present in stems and, to a lesser extent, roots. Deletion analyses identified the region between -818 and -513 as essential for high-level, temporally regulated expression in seeds and also indicated that the sequence between -513 and -356 plays a negative role in leaf/stem, but not seed, expression. Comparison of translational and transcriptional fusions indicated that the LOX initiation codon was used more efficiently than the GUS initiation codon by the tobacco leaf translational apparatus.

Base Sequence↗
PubMed1994

Measurement of angiotensin II: use of two injectors to minimize HPLC shadowing.

We investigated the use of two HPLC injectors, one reserved for standards and the other for blanks or biological samples, to minimize shadowing in the measurement of angiotensin II (ANGII). HPLC carryover of standard ANGII to blank with a one-injector and a two-injector system were 47.0 +/- 5.0 and 2.4 +/- 0.5 fmol/ml, respectively, a 19.6-fold reduction. Measured normal canine left ventricular myocardium ANGII level by the two-injector HPLC-RIA system was 22.3 +/- 2.4 fmol/g, with a signal-to-noise ratio of 11.7, an improved signal-to-noise ratio of 29.3 fold vs. the one injector. This innovation reduced the incidence of false-positive ANGII results, and thus can be applied to other compounds that exhibit HPLC-derived shadowing.

Angiotensin II↗
PubMed1994

Noradrenaline biosynthesis and metabolism during development and recovery from pacing-induced heart failure in the dog.

We have modified an assay utilizing ion-pair high-performance liquid chromatography with electrochemical detection to measure dihydroxyphenylalanine and dyhydroxyphenylglycol simultaneously with noradrenaline. We measured these agents at control, 1 and 3 weeks following the onset of rapid ventricular pacing, as well as 4 weeks after the cessation of a 3-week period of pacing. Our findings were as follows. Plasma noradrenaline increased significantly at 1 week and increased further after 3 weeks of pacing (control, 202 +/- 16; 1 week, 528 +/- 62; 3 weeks, 750 +/- 139 pg.mL-1). Plasma dihydroxyphenylalanine did not change throughout, while plasma dihydroxyphenylglycol was significantly elevated at 3 weeks (513 +/- 48 vs. 388 +/- 35 pg.mL-1 for the control). Four weeks after discontinuation of pacing, all parameters did not differ from the control. These results imply that during the development of heart failure, the rise in circulating noradrenaline does not reflect simply an increase in catecholamine synthesis, but that there are more dynamic changes associated with noradrenaline spill-over, uptake, and metabolism.

Animals↗
PubMed1994

Myocardial beta-adrenoceptors in pacing-induced heart failure: regulation by enalapril?

In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.

Angiotensin II↗
PubMed1994

Endothelium-dependent relaxations in canine coronary arteries are enhanced in early heart failure and persist in recovery.

In vitro coronary artery responsiveness to noradrenaline, phenylephrine, and BHT-920 together with functional relaxation to acetylcholine was assessed in dogs at the early onset of pacing-induced heart failure (1 week) and in dogs recovered from heart failure (3 weeks paced, followed by 4 weeks discontinued pacing). alpha-Adrenoceptor stimulation produced contractile responses that were unaltered in early congestive heart failure and recovery. Contractions to noradrenaline and BHT-920 were always less than those produced by phenylephrine. Endothelium-intact arteries demonstrated relaxations in response to noradrenaline and BHT-920, but not phenylephrine. Relaxations to noradrenaline were enhanced 24% in early heart failure and 47% following recovery from heart failure, compared with control. BHT-920 produced relaxations that were augmented 21 and 76% in early heart failure and recovery, respectively. Contractile sensitivity to noradrenaline increased 5-fold in early heart failure and was not different in recovery, compared with control. Contractile sensitivity to BHT-920 and phenylephrine was unaltered throughout. Acetylcholine produced relaxations that were increased 21% in early heart failure and 13% after recovery from congestive heart failure. Furthermore, acetylcholine sensitivity was significantly enhanced in early heart failure and recovery. The current study reveals a progressive adaptation of the coronary endothelium in congestive heart failure, possibly directed towards protection against excessive vasoconstriction due to circulating catecholamines.

Acetylcholine↗
PubMed1994

Psychological and sexual changes after the cessation of breast-feeding.

OBJECTIVE: To characterize the effect of breast-feeding cessation on the mood and sexuality of women after the birth of their first child. METHODS: Women in good physical and psychological health, who had been breast-feeding for 6-23 months and had responded to a request for subjects in a parents' magazine, collected data daily for 2 months before and 2 months after weaning. They were asked to rate 14 measures of psychological, physical, and sexual variables at the same time each day on 3- or 5-point scales. RESULTS: Nineteen women completed the study. Five of these subjects became pregnant before weaning and ceased breast-feeding when pregnancy was confirmed; their last menstrual period was 6 weeks before weaning. The non-pregnant women weaned their babies just before or during menstruation. After weaning, the nonpregnant women reported a significant decrease in fatigue, improvement in mood, and an increase in sexual activity, sexual feelings, and frequency of coitus. Significant changes in fatigue and mood occurred during the second week after weaning; in fatigue, sexual activity, and sexual intercourse during the third week; and in the frequency of sexual intercourse in the fourth week. THe results were not caused by the subjects' expectations about breast-feeding and sexuality or perineal comfort. The women who conceived did not show these changes; a gradual increase in fatigue and decline in sexuality was observed. CONCLUSION: In women who are not pregnant, the cessation of breast-feeding is associated with an improvement in mood, fatigue, and sexuality.

Adult↗
PubMed1993

Nifedipine inhibits responses to alpha-adrenoceptor stimulation in canine blood vessels: impact of heart failure.

The effects of nifedipine (10(-8) and 10(-7) M) on alpha-adrenergic responses of the dorsal pedal artery and saphenous vein were examined from dogs with pacing-induced heart failure. Two groups of dogs had their right ventricles paced at 250 beats/min: group (1) 1 week of pacing (mild heart failure) and group (2) paced for a mean period of 25.8 days (peak heart failure). Nifedipine non-competitively antagonised 6-allyl-2-amino-5,6,7,8-tetrahydro-4H- thiazolo[4,5-d]azepin dihydrochloride (BHT 920)-induced contractions to the same extent (i.e. at control, mild heart failure and peak heart failure) and IC50 values were as follows: for dorsal pedal artery 3.9 (1.8-6.1) nM, 4.4 (1.2-8.4) nM and 8.5 (2.9-38.9) nM, respectively; for saphenous vein 13.0 (4.6-26.0) nM, 13.0 (7.3-18.6) nM and 19.0 (9.3-32.8) nM, respectively). Before the onset of pacing, nifedipine did not affect concentration-effect curves generated to noradrenaline or phenylephrine in either the artery or the vein. After 1 week of pacing, nifedipine (10(-7) M) inhibited contractions to noradrenaline in the artery and the vein (70 +/- 5% for the artery and 51 +/- 4% for the vein). Nifedipine had no effect on phenylephrine-induced contractions. At peak heart failure, nifedipine inhibited both noradrenaline and phenylephrine contractions. These results indicate that nifedipine is useful in differentiating contractile activity of vascular smooth muscle with respect to alpha-adrenoceptor agonism.

Animals↗
PubMed1993

Beta adrenoceptor recovery after heart failure in the dog.

OBJECTIVE: The role of myocardial beta receptors in pacing induced congestive heart failure is uncertain. The aims of the study were therefore (1) to examine total beta adrenoceptor density in canine left ventricle during pacing induced heart failure; and (2) to evaluate whether there is a relationship between beta adrenoceptor numbers and circulating noradrenaline during progression of heart failure. METHODS: Heart failure was examined at different stages: early (after 1 week of pacing at 250 beats.min-1); peak (after 4 weeks of pacing); and after recovery (4 weeks after pacing was discontinued). Myocardial beta adrenoceptor density was assessed by radioligand binding with iodocyanopindolol. Plasma noradrenaline was determined by high performance liquid chromatography with electrochemical detection. RESULTS: Compared to control, left ventricular beta adrenoceptor density was: (1) not significantly different in early heart failure, at 2540(SEM 460) v 3160(260) fmol.g-1 wet weight in control; (2) decreased 63% at peak heart failure [1180(100) fmol.g-1, p < 0.01]; and (3) restored to control density after recovery from heart failure [3430(540) fmol.g-1]. The beta adrenoceptor dissociation constant was unaltered throughout. There was an inverse correlation between myocardial beta adrenoceptor density and plasma noradrenaline (r = -0.785, p < 0.01). CONCLUSIONS: The progressive decline in beta adrenoceptor density as heart failure develops and the capacity of beta adrenoceptors to return to control levels after recovery from the experimental heart failure state suggests that there is a reversible abnormality in beta adrenoceptors during heart failure.

Animals↗
PubMed1992

Differential effects of dipyrone, ibuprofen, and paracetamol on experimentally induced pain in man.

In a double-blind cross-over study on 22 healthy subjects the analgesic efficacies of the antipyretic analgesic drugs ibuprofen, dipyrone and paracetamol were tested against placebo using a model of experimentally induced pain. To this purpose interdigital webs were pinched repeatedly for 2 min periods. The painfulness of these stimuli was assessed by the subjects on an electronically controlled visual analogue scale at 10 sec intervals. In addition to the subjective pain ratings the stimulus induced reflex diminution of the blood flow in the stimulated hand was measured with photoplethysmography and laser Doppler flow analysis. The flare response around the stimulated area was assessed with infrared thermography. In this assay system ibuprofen and dipyrone, but not paracetamol, showed statistically significant analgesic effects by preventing hyperalgesia which is normally induced by the repeated stimulation of a skin site. This hypoalgesic effect was not related to the subjective impression of the subjects of the analgesic potency of the respective drug. Sympathetic reflex vasoconstriction was not quantitatively related to the drug induced hypoalgesia. Ibuprofen and, to a minor extent, the other antipyretic analgesic drugs also diminished the stimulus induced flare reaction around the stimulated skin sites.

Acetaminophen↗
PubMed1992

Impaired vascular reactivity following angioplasty is mainly due to endothelial injury.

Vasoconstriction occurs frequently following coronary angioplasty and is implicated in the pathogenesis of abrupt closure and restenosis. Control of vasomotor tone is regulated in part directly by smooth muscle cells and indirectly through the endothelium. To study the mechanisms underlying vasoconstriction, the effect of angioplasty and endothelial denudation on endothelium-dependent and -independent relaxation was examined in 15 mongrel dogs. Percutaneous transluminal angioplasty and endothelial denudation of the right femoral artery were performed. Endothelial injury was assessed by adhesion of indium-111-labeled platelets. Endothelium-dependent and -independent relaxation were assessed using acetylcholine and nitroglycerin, respectively. Vessels precontracted with potassium chloride and exposed to acetylcholine showed impaired relaxation in both the angioplasty and denuded groups (angioplasty = 14 +/- 5%, denuded = 0 +/- 0%, normal = 73 +/- 12%; P less than 0.05 for both angioplasty and denuded compared to normal). Precontraction with phenylephrine yielded similar results (angioplasty = 16 +/- 8%, denuded = 4 +/- 2%, normal = 39 +/- 10%; P less than 0.05 only for denuded segment compared to normal). Segments precontracted with phenylephrine and exposed to nitroglycerin did not demonstrate impaired relaxation (angioplasty = 73 +/- 9%, denuded = 68 +/- 9%, normal = 71 +/- 7%, P = ns). Mean indium-111 counts were similar in both the angioplasty and denuded segments (2820 +/- 1481 and 2963 +/- 1228 counts/min/g, respectively) compared to a lower count in the normal segment (1514 +/- 956 counts/min/g). Thus, angioplasty produces significant vascular injury and impairment of vasodilator function, comparable to that caused by endothelial denudation alone. This implies that vasoconstriction seen following coronary angioplasty may be due to endothelial injury and the resultant loss of control of vasomotor tone.

Acetylcholine↗
PubMed1992

Temporal alterations in peripheral vascular responsiveness during both the development and recovery from pacing-induced heart failure.

The responsiveness of both the in vitro dorsal pedal artery and in vitro saphenous vein to alpha-adrenergic agents and prostaglandin F2 alpha was evaluated at baseline (prior to the onset of rapid ventricular pacing), at 1 week of pacing (mild heart failure), and 4 weeks after pacing when there was recovery from congestive heart failure. Eleven dogs were paced at 250 beats/min for 1 week and 7 dogs were paced for 3 weeks at 250 beats/min and allowed to recover from pacing for a further 4 weeks. At 1 and 4 weeks of recovery, compared to control, the maximal responsiveness of the dorsal pedal artery to norepinephrine was increased from 5.7 +/- 0.9 to 12.9 +/- 3.3 and 18.6 +/- 1.0 g/mm2, respectively. A similar finding was observed in the saphenous vein. The response of the artery to the selective alpha 1-agonist, phenylephrine, was also enhanced at 1 week. Moreover, the response of the artery and vein to phenylephrine was enhanced further at 4 weeks of recovery. In contrast, the response to the selective alpha 2-agonist, BHT 920, remained unaltered at these time points compared to control. Oxymetazoline, an agent used to differentiate between alpha 1-subdivisions, produced a significantly higher maximal response at 4 weeks of recovery (18.4 +/- 1.6 g/mm2 for the artery and 27.7 +/- 2.6 g/mm2 for the vein) compared to control (8.2 +/- 0.5 g/mm2 for the artery and 10.3 +/- 0.8 g/mm2 for the vein). The artery also displayed lower EC50 values for norepinephrine and phenylephrine at 1 week (0.7 and 2.2 microM, respectively) and 4 weeks of recovery (0.9 and 3.1 microM, respectively) compared to control (6.0 and 9.0 microM, respectively). In contrast, the only significant decreases in EC50's in the vein were the norepinephrine and oxymetazoline at 1 week of pacing (0.2 and 0.06 microM, respectively) compared to control (1.5 and 0.09 microM, respectively). The maximal tension developed to PGF2 alpha was enhanced after 1 week of pacing in both vessels and persisted 4 weeks following the cessation of pacing. Compared with control, EC50 values for PGF2 alpha were decreased at 1 and 4 weeks of recovery. We conclude that differences exist in peripheral vascular reactivity to both alpha 1-adrenoceptor agents and PGF2 alpha at 1 week of pacing and 4 weeks of recovery from pacing. Furthermore, the subtle reactivity differences between the artery and vein reflect different populations of alpha 1-adrenoceptors possibly associated with different signal transduction processes.

Adrenergic alpha-Agonists↗
PubMed1992

Impact of enalapril therapy on in vitro coronary artery responsiveness in pacing-induced heart failure.

In vitro coronary artery responsiveness to angiotensin I, angiotensin II, noradrenaline, phenylephrine, BHT 920, and potassium chloride together with functional relaxation to acetylcholine was investigated in dogs with pacing-induced heart failure treated with enalapril (oral administration of 10 mg.day-1) for a mean duration of 26 days. Although maximal responses generated to both angiotensin I and angiotensin II were unaltered in the enalapril-treated group, angiotensin II became more potent following enalapril treatment: the EC50 for angiotensin II following placebo treatment was 2.4 (0.6-5.8; 95% confidence limits) nM and following enalapril treatment was 0.03 (0.007-0.1; 95% confidence limits) nM. In addition to the above changes, coronary artery rings from dogs treated with enalapril developed significantly less tension to noradrenaline, phenylephrine, and BHT 920. In contrast, responses to potassium chloride were unaltered following enalapril treatment. However, the relaxation to acetylcholine was enhanced from 38.9 +/- 3.0 to 50.4 +/- 3.5% (placebo versus enalapril, p < 0.05). These findings indicate that enalapril may possess alpha-blocking properties and enhance the relaxation response to acetylcholine through an endothelial-dependent mechanism in addition to inhibiting converting enzyme.

Acetylcholine↗
PubMed1991

Novel vascular effects of isoprenaline following pacing-induced heart failure in the dog.

Isoprenaline produced concentration-dependent contractions of the in vitro canine saphenous vein which were attenuated by phentolamine (10(-6) M) and pacing-induced heart failure. Both at control and peak heart failure, a biphasic response was seen in the dorsal pedal artery, consisting of an initial relaxation followed by a contraction; phentolamine and heart failure enhanced the relaxation component. In the presence of propranolol, the isoprenaline-induced contraction was sensitive to yohimbine, but resistant to prazosin. Therefore it is concluded that isoprenaline interacts not only with vascular beta-adrenoceptors, but also with alpha 2-adrenoceptors. Endothelial denudation resulted in a diminished response to isoprenaline in control saphenous vein and dorsal pedal artery but not in vessels from dogs with heart failure. The observation that the contractile response to isoprenaline diminishes in heart failure implies a specific down-regulation of peripheral vascular alpha 2-adrenoceptors.

Adrenergic Antagonists↗