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1.
Phys Rev Lett ; 125(15): 155003, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33095614

ABSTRACT

The implosion efficiency in inertial confinement fusion depends on the degree of stagnated fuel compression, density uniformity, sphericity, and minimum residual kinetic energy achieved. Compton scattering-mediated 50-200 keV x-ray radiographs of indirect-drive cryogenic implosions at the National Ignition Facility capture the dynamic evolution of the fuel as it goes through peak compression, revealing low-mode 3D nonuniformities and thicker fuel with lower peak density than simulated. By differencing two radiographs taken at different times during the same implosion, we also measure the residual kinetic energy not transferred to the hot spot and quantify its impact on the implosion performance.

2.
Phys Rev E ; 110(1): L013201, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39161029

ABSTRACT

The predicted implosion performance of deuterium-tritium fuel capsules in indirect-drive inertial confinement fusion experiments relies on precise calculations of the x-ray drive in laser-heated cavities (hohlraums). This requires accurate, spectrally dependent simulations of laser to x-ray conversion efficiencies and x-ray absorption losses to the hohlraum wall. A set of National Ignition Facility experiments have identified a cause for the long-standing hohlraum "drive deficit" as the overprediction of gold emission at ∼2.5 keV in nonlocal thermodynamic equilibrium coronal plasma regions within the hohlraum. Reducing the emission and absorption opacity in this spectral region by ∼20% brings simulations into agreement with measured x-ray fluxes and spectra.

3.
Semin Immunopathol ; 45(3): 389-410, 2023 05.
Article in English | MEDLINE | ID: mdl-37273022

ABSTRACT

Despite years of encouraging translational research, ischemic stroke still remains as one of the highest unmet medical needs nowadays, causing a tremendous burden to health care systems worldwide. Following an ischemic insult, a complex signaling pathway emerges leading to highly interconnected thrombotic as well as neuroinflammatory signatures, the so-called thromboinflammatory cascade. Here, we thoroughly review the cell-specific and time-dependent role of different immune cell types, i.e., neutrophils, macrophages, T and B cells, as key thromboinflammatory mediators modulating the neuroinflammatory response upon stroke. Similarly, the relevance of platelets and their tight crosstalk with a variety of immune cells highlights the relevance of this cell-cell interaction during microvascular dysfunction, neovascularization, and cellular adhesion. Ultimately, we provide an up-to-date overview of therapeutic approaches mechanistically targeting thromboinflammation currently under clinical translation, especially focusing on phase I to III clinical trials.


Subject(s)
Stroke , Thrombosis , Humans , Inflammation , Thrombosis/etiology , Stroke/therapy , Blood Platelets , Signal Transduction
4.
Nat Commun ; 14(1): 7046, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37949859

ABSTRACT

Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.

5.
Rev Sci Instrum ; 89(10): 10K111, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30399855

ABSTRACT

Achieving a symmetric implosion in National Ignition Facility indirect drive targets requires understanding and control of dynamic changes to the laser power transport in the hohlraum. We developed a new experimental platform to simultaneously visualize wall-plasma motion and dynamic laser power transport in the hohlraum and are using it to investigate correlations of these measurements with the imploded capsule symmetry. In a series of experiments where we made one single parameter variation, we show the value of this new platform in developing an understanding of laser transport and implosion symmetry. This platform also provides a new way to evaluate dynamic performance of advanced hohlraum designs.

6.
Rev Sci Instrum ; 87(11): 11E321, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27910418

ABSTRACT

The high fuel capsule compression required for indirect drive inertial confinement fusion requires careful control of the X-ray drive symmetry throughout the laser pulse. When the outer cone beams strike the hohlraum wall, the plasma ablated off the hohlraum wall expands into the hohlraum and can alter both the outer and inner cone beam propagations and hence the X-ray drive symmetry especially at the final stage of the drive pulse. To quantitatively understand the wall motion, we developed a new experimental technique which visualizes the expansion and stagnation of the hohlraum wall plasma. Details of the experiment and the technique of spectrally selective x-ray imaging are discussed.

7.
Peptides ; 11(5): 939-44, 1990.
Article in English | MEDLINE | ID: mdl-2178251

ABSTRACT

The biological activity of thyrotropin-releasing hormone (TRH) and its analogs 4(5)-I-Im-TRH and 2,4(5)-I2-Im-TRH was assessed by means of their effects on: 1) the mean arterial pressure (MAP), 2) heart rate (HR), 3) ventilation minute volume (MV), 4) contractility of the rat duodenum, and 5) concentrations of thyrotropin (TSH) or prolactin (PRL) in serum. Also their binding to TRH-receptors in brain homogenates was studied. In urethane-anesthetized rats TRH ICV increased MAP, HR and MV. 4(5)-I-Im-TRH was equally as active as TRH on HR and MV but a significant elevation in MAP was observed only at a dose 100-fold to that of TRH. However, the maximal responses of 4(5)-I-Im-TRH and TRH did not differ. In conscious rats, TRH 1A elevated MAP and HR but 4(5)-I-Im-TRH was active on MAP only. 2,4(5)-I2-Im-TRH was devoid of cardiorespiratory activity. TRH dose-dependently inhibited the contractions of the rat duodenum while the iodinated analogs lacked such an activity. To induce a significant release of TSH several hundred times more of 4(5)-I-Im-TRH and over 1000 times more of 2,4(5)-I2-Im-TRH were needed as compared to TRH. The iodoanalogs elevated PRL levels only at doses 2000-fold higher than those of TRH. The iodoanalogs displaced [3H][3-Me-His2]TRH [( 3H]MeTRH) from its binding sites at concentrations about 1000 times higher than those of TRH. Substitutions of the histidyl moiety of TRH in 4(5)-I-Im-TRH and 2,4(5)-I2-Im-TRH resulted in substantial loss of the endocrine activity. While the di-iodinated analog was practically devoid of any biological activity the monoiodinated analog exerted similar cardiorespiratory activity to that of TRH.


Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Lung Volume Measurements , Thyrotropin-Releasing Hormone/analogs & derivatives , Thyrotropin-Releasing Hormone/pharmacology , Animals , Duodenum/drug effects , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Prolactin/metabolism , Rats , Rats, Inbred Strains , Receptors, Neurotransmitter/drug effects , Receptors, Thyrotropin-Releasing Hormone , Thyrotropin/metabolism
8.
Neuropeptides ; 18(2): 93-8, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1901964

ABSTRACT

Thyrotropin-releasing hormone was shown to exert potent ventilatory effects after central administration. These data, however, were derived from studies using anesthetized animal preparations. Since TRH elicits strong arousal reactions, the observed ventilatory effects of TRH under anesthesia may have been due to nonspecific reduction in the anesthetic state of the animals. In order to clarify the extent to which the reversal of anesthesia may change ventilatory parameters after TRH application, we investigated the effect of TRH on ventilation rate, relative tidal volume, relative respiratory minute volume, CO2 production CO2 consumption, and locomotor activity in the conscious, unrestrained rat. Intracerebroventricular application of TRH induced a dose-dependent, sustained increase in ventilation rate, relative tidal volume, and relative respiratory minute volume of maximally 128%, 890%, and 235%, respectively. In addition, CO2 production and O2 consumption were elevated by 4.6 and 11.7 fold, while no significant changes in locomotor activity were observed. The results suggest that TRH stimulates ventilation by a mechanism independent of its analeptic properties.


Subject(s)
Cerebral Ventricles/physiology , Respiration/drug effects , Thyrotropin-Releasing Hormone/pharmacology , Animals , Carbon Dioxide/metabolism , Cerebral Ventricles/drug effects , Injections, Intraventricular , Male , Motor Activity/drug effects , Oxygen Consumption/drug effects , Rats , Rats, Inbred Strains , Reference Values , Thyrotropin-Releasing Hormone/administration & dosage , Tidal Volume/drug effects
9.
Eur J Pharmacol ; 180(1): 1-12, 1990 May 03.
Article in English | MEDLINE | ID: mdl-2163861

ABSTRACT

Norvaline2-thyrotropin-releasing hormone ([Nva2]TRH) has been described as a thyrotropin-releasing hormone (TRH) analog with no thyrotropin (TSH)-releasing capacity but enhanced analeptic activity compared with TRH, as shown by the reversal of haloperidol-induced catalepsy. We have evaluated the receptor-binding properties of [Nva2]TRH in homogenates of rat anterior pituitary, hypothalamus, brainstem and cortex tissue, using [3H]TRH and [3H][3-Me-His2]TRH as radioligands. Apparent Ki values at high affinity TRH-binding sites, labelled predominantly by [3H][3-Me-His2]TRH, ranged from 17.0 to 36.9 microM in all tested regions. Additionally, [Nva2]TRH was shown to compete with [3H]TRH at low affinity TRH-binding sites with similar affinities. It is concluded that the loss of TSH-releasing activity of [Nva2]TRH appears to be due to a drastic reduction in binding affinity to the high affinity TRH receptor subtype. Its analeptic activity, however, may be mediated by low affinity TRH binding sites which are predominantly labelled by [3H]TRH or by yet unidentified mechanisms.


Subject(s)
Brain/metabolism , Receptors, Neurotransmitter/metabolism , Thyrotropin-Releasing Hormone/analogs & derivatives , Animals , Binding, Competitive/drug effects , Brain/drug effects , Brain Stem/drug effects , Brain Stem/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Filtration , Hypothalamus/drug effects , Hypothalamus/metabolism , In Vitro Techniques , Kinetics , Male , Pyrrolidonecarboxylic Acid/analogs & derivatives , Rats , Rats, Inbred Strains , Receptors, Thyrotropin-Releasing Hormone , Thyrotropin-Releasing Hormone/metabolism
10.
Eur J Pharmacol ; 164(1): 77-83, 1989 May 02.
Article in English | MEDLINE | ID: mdl-2753081

ABSTRACT

Binding properties of [4(5)-fluoro-imidazole-His2]-TRH (4(5)-F-TRH), [2-trifluoromethyl-imidazole-His2]-TRH (2-CF3-TRH) and [4(5)-trifluoromethyl-imidazole-His2]-TRH (4(5)-CF3-TRH), three novel TRH analogs, have been evaluated in rat pituitary, hypothalamus, brainstem and cortex tissue. 4(5)-F-TRH, previously shown to elicit arterial pressor responses and prolactin release similar to those of TRH, binds to TRH receptors with low, micromolar affinity (Ki = 7.5-13.5 microM). 2-CF3-TRH, an analog of less cardiovascular but increased prolactin-releasing activity, shows Ki values of 3.3-4.9 microM. 4(5)-CF3-TRH, which shows comparable biological activity to 2-CF3-TRH, demonstrates a binding affinity which is virtually nonspecific (Ki = 0.39-1.01 mM). It is therefore concluded that the biological effects of these analogs are mediated either through low affinity TRH binding sites not recognized by [3H][3Me-His2]-TRH or through mechanisms not involving TRH receptors as such.


Subject(s)
Brain/metabolism , Histidine/analogs & derivatives , Histidine/pharmacology , Receptors, Thyroid Hormone/metabolism , Animals , Binding, Competitive/drug effects , Brain/drug effects , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Rats , Rats, Inbred Strains , Receptors, Thyroid Hormone/drug effects , Time Factors
11.
Eur J Pharmacol ; 416(1-2): 83-93, 2001 Mar 23.
Article in English | MEDLINE | ID: mdl-11282116

ABSTRACT

The binding of Tyr-D-Arg(2)-Phe-sarcosine(Sar)(4) (TAPS), a proposed mu-opioid receptor-selective tetrapeptide analog of dermorphin to opioid receptors, was studied using selective binding assays for subtypes of mu-, delta- and kappa-opioid receptors. Subtype specific mu-opioid receptor binding was further characterized in the presence of sodium and guanosine nucleotides and the activity of TAPS in isolated guinea pig ileum was compared to other mu-opioid receptor-selective ligands. Further, the antinociceptive properties of TAPS following intrathecal (i.t.) administration in rats, as a model of spinal antinociception, were evaluated. The K(i)-values for TAPS at the mu(1)- and mu(2)-opioid receptor sites were 0.4 and 1.3 nM, respectively, suggesting high affinity binding to mu-opioid receptor binding sites with an increased selectivity to mu(1)-opioid receptor sites. The attenuated reduction of TAPS binding at the mu(2)-opioid receptor subtype in the presence of the stable guanosintriphosphate analog 5'-guanylylimidodiphosphate and sodium suggests a potential partial antagonist mode of action at this site.


Subject(s)
Analgesics/pharmacology , Naloxone/analogs & derivatives , Oligopeptides/pharmacology , Receptors, Opioid/metabolism , Animals , Binding, Competitive/drug effects , Catalepsy/chemically induced , Dose-Response Relationship, Drug , Electric Stimulation , Guinea Pigs , Ileum/drug effects , Ileum/physiology , In Vitro Techniques , Injections, Spinal , Male , Muscle Contraction/drug effects , Naloxone/pharmacology , Nociceptors/drug effects , Oligopeptides/chemistry , Oligopeptides/metabolism , Opioid Peptides , Pulmonary Ventilation/drug effects , Radioligand Assay , Rats , Rats, Sprague-Dawley , Time Factors
12.
Neurosci Lett ; 113(2): 187-92, 1990 May 31.
Article in English | MEDLINE | ID: mdl-2115985

ABSTRACT

The present study was performed to quantify the distribution of a peptide neurotransmitter after microinjection into the medial preoptic area (POM), using a technique suitable for conscious animal preparations. The results indicate that only 50-nl volumes of injected tracer were sufficiently localized with 77 +/- 9% recovery in the POM. Injections of higher volumes resulted in an increasing spread of tracer into distant anatomical regions and structures, including the needle tract and cerebral ventricles. The amount of tracer localized in the POM decreased to 38 +/- 4% (200 nl) (P less than 0.05) and 14 +/- 8% (500 nl) (P less than 0.05), respectively. The data suggest that the volume of injection is critical for intraparenchymal injections into structures of a diameter of 1mm or less, such as the POM and should not exceed 50 nl in conscious animal preparations.


Subject(s)
Microinjections , Preoptic Area/metabolism , Thyrotropin-Releasing Hormone/pharmacokinetics , Animals , Autoradiography , Male , Rats , Rats, Inbred Strains
13.
Life Sci ; 49(2): 111-9, 1991.
Article in English | MEDLINE | ID: mdl-1676481

ABSTRACT

The present study was performed in order to evaluate the effects of the selective alpha 2-adrenoceptor antagonist 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine (SK&F 86466) on dermorphin-induced analgesia, respiratory depression and inhibition of locomotor activity in the conscious rat. Intracerebroventricular (icv) administration of dermorphin (3 nmol/rat) decreased respiration rate and relative ventilatory minute volume maximally by 38% and 50% of baseline respectively. SK&F 86466 dose-dependently reversed the dermorphin-induced depression of ventilatory parameters, while SK&F 86466 exerted no effect on dermorphin-induced analgesia or depression of locomotor activity due to catalepsia. It appears, therefore, that alpha 2-adrenoceptors selectively interact with mu 2-opioid-receptor mediated effects, such as respiratory depression, but are not involved in the modulation of mu 1-opioid-related effects, such as supraspinal analgesia and depression of locomotor activity.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Analgesics, Opioid/pharmacology , Benzazepines/pharmacology , Oligopeptides/pharmacology , Receptors, Opioid/physiology , Respiration/drug effects , Amino Acid Sequence , Animals , Injections, Intraventricular , Male , Molecular Sequence Data , Motor Activity/drug effects , Oligopeptides/administration & dosage , Opioid Peptides , Oxygen Consumption/drug effects , Rats , Rats, Inbred Strains , Receptors, Opioid, mu
14.
Int J Cardiol ; 63(3): 237-44, 1998 Feb 28.
Article in English | MEDLINE | ID: mdl-9578350

ABSTRACT

OBJECTIVE: To investigate plasma tumor necrosis factor (TNF)alpha, tumor necrosis factor alpha soluble receptor I, interleukin-1beta and neopterin concentrations as markers of monocyte activation in patients with heart failure. STUDY DESIGN: The group consisted of patients with heart failure due to dilated cardiomyopathy (n=19) and coronary artery disease (n=11). Patients without cardiac failure served as controls (n=10). RESULTS: TNFalpha concentrations were elevated only in heart failure patients with coronary artery disease (2.9+/-0.3 pg/ml versus 1.7+/-0.3 pg/ml; P<0.05). When the patients were grouped according to acute and chronic failure, TNFalpha concentrations were significantly elevated in acute failure (3.1+/-0.4 pg/ml, n=6 versus 1.7+/-0.2 pg/ml, n=8; P<0.05). TNFalpha concentrations were elevated in patients with coronary artery disease and chronic heart failure compared to coronary artery disease patients without failure (2.0+/-0.4 pg/ml, n=6 versus 1.8+/-0.3 pg/ml, n=7; P<0.05). A higher proportion of patients with myocardial insufficiency showed increased lipopolysaccharide-inducible TNFalpha concentrations (10/30 versus 0/9, P<0.05). CONCLUSIONS: TNFalpha is elevated in patients with acute cardiac decompensation. Among patients with chronic heart failure only those with coronary artery disease exhibit increased levels. Cytokine concentrations are similar in heart failure due to dilated cardiomyopathy and coronary artery disease. Monocytes of patients suffering from cardiac insufficiency show an increased sensitivity towards stimuli such as lipopolysaccharides.


Subject(s)
Cardiomyopathy, Dilated/blood , Coronary Disease/blood , Heart Failure/blood , Monocytes/physiology , Tumor Necrosis Factor-alpha/analysis , Biomarkers , Cardiomyopathy, Dilated/complications , Heart Failure/etiology , Heart Failure/physiopathology , Hemodynamics , Humans , Interleukin-1/analysis , Middle Aged , Receptors, Tumor Necrosis Factor/blood
15.
Acta Cardiol ; 54(2): 83-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10378019

ABSTRACT

BACKGROUND: Enteroviruses were detected in up to 50% in myocardium of patients with myocarditis and dilated cardiomyopathy, the latter being considered as a result of a prior subclinical myocarditis. A wide range of other infectious agents are being discussed as pathogens, often only based on reports of single cases. Adenovirus genome was recently identified in a significant number in the myocardium of paediatric patients with myocarditis. However, data on the role of adenoviruses for the aetiopathogenesis of myocarditis in adult patients is missing so far. Therefore, we studied the prevalence of adenoviral and enteroviral genome in myocardium of adults with myocarditis and dilated cardiomyopathy. METHODS: 15 patients were diagnosed at baseline with myocarditis, 16 patients with dilated cardiomyopathy according to clinical and histological criteria. Endomyocardial biopsies of these patients and 8 control patients with non-infectious heart diseases were evaluated by polymerase chain reactions for enterovirus and adenovirus genome. RESULTS: Enteroviral genome was detected in 27.3% patients with myocarditis or dilated cardiomyopathy, whereas adenoviral genome was not identified in any patient. Samples from control subjects systematically yielded negative results. CONCLUSIONS: From our data, it seems doubtful that adenoviruses are major pathogens of myocarditis or DCM, whereas enterovirus genome was identified in a significant number of patients with both diseases.


Subject(s)
Adenovirus Infections, Human/diagnosis , Adenoviruses, Human/pathogenicity , Cardiomyopathy, Dilated/diagnosis , Enterovirus Infections/diagnosis , Enterovirus/pathogenicity , Myocarditis/diagnosis , Adenovirus Infections, Human/pathology , Adenovirus Infections, Human/virology , Adenoviruses, Human/genetics , Adult , Aged , Cardiomyopathy, Dilated/pathology , Cardiomyopathy, Dilated/virology , Endocardium/pathology , Endocardium/virology , Enterovirus/genetics , Enterovirus Infections/pathology , Enterovirus Infections/virology , Female , Gene Expression/physiology , Genes, Viral/genetics , Humans , Male , Middle Aged , Myocarditis/pathology , Myocarditis/virology , Myocardium/pathology , Polymerase Chain Reaction , Prospective Studies , Virulence/genetics
16.
Pharmacol Toxicol ; 69(5): 322-6, 1991 Nov.
Article in English | MEDLINE | ID: mdl-1803344

ABSTRACT

The modulation of cardioventilator effects of thyrotropin-releasing hormone (TRH) by histaminergic mechanisms was studied in anaesthetized rats pretreated with histamine receptor antagonists. TRH (1-100 nmol/kg) into the lateral cerebral ventricle dose-dependently elevated mean arterial pressure, heart rate and stimulated respiration. The respiratory stimulating effect of TRH remained unchanged after pretreatments with histamine H1-receptor antagonist diphenhydramine or H2-receptor antagonists cimetidine and ranitidine, while the TRH-induced hypertension and tachycardia were attenuated by cimetidine. This antagonism was not due to an interaction between TRH and cimetidine at their central binding sites, since there was no displacement of [3H]MeTRH binding in the presence of cimetidine nor did TRH displace [3H]cimetidine in rat brain homogenates. Inability of diphenhydramine to modify the cardiovascular effects of TRH indicates that these effects are not due to histamine liberation, as cardiovascular stimulation after central administration of histamine is mainly mediated via H1-receptors. The antagonism of the cardiovascular responses to TRH by cimetidine was not due to blockade of H2-receptors, since another potent H2-receptor antagonist ranitidine was unable to affect the cardiovascular effects of TRH. Therefore, we suggest that cimetidine exerted antagonism of TRH by some non-specific action.


Subject(s)
Cimetidine/pharmacology , Hemodynamics/drug effects , Thyrotropin-Releasing Hormone/antagonists & inhibitors , Animals , Binding Sites/drug effects , Brain/drug effects , Diphenhydramine/pharmacology , Dose-Response Relationship, Drug , Histamine/metabolism , Male , Ranitidine/pharmacology , Rats , Rats, Inbred Strains , Respiration/drug effects , Thyrotropin-Releasing Hormone/pharmacology
17.
Am J Physiol ; 261(2 Pt 2): R305-12, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1678932

ABSTRACT

The role of thyrotropin-releasing hormone (TRH) and glutamate in central cardiovascular control was studied by microinjections (50 nl) of these agents into the medial or median preoptic nuclei of conscious rats (n = 49) with continuous recording of mean arterial pressure, heart rate, blood flow, and vascular resistance in hindquarter, renal, and mesenteric blood vessels. In addition, the effect of TRH on renal sympathetic nerve activity was studied in anesthetized rats. TRH (2.4-240 pmol) elicited the typical hemodynamic pattern of the "defense response" consisting of increased blood pressure, tachycardia, hindquarter vasodilation, and constriction of renal and mesenteric blood vessels. Maximum changes in cardiovascular variables after the 24-pmol dose were +12 +/- 2 mmHg (mean arterial pressure), +73 +/- 15 beats/min (heart rate), -21 +/- 6% (hindquarter resistance), +15 +/- 6% (renal resistance), and +31 +/- 6% (mesenteric resistance), P less than 0.05 compared with saline. In anesthetized rats, TRH at the 2.4-pmol dose increased renal sympathetic nerve activity (greater than 200%, n = 5, P less than 0.05 compared with control) with no effect on blood pressure or renal flow. Glutamate (10 or 100 nmol) produced a similar pattern of hemodynamic changes as TRH. Peak effects after the 100-nmol dose of glutamate were +16 +/- 2 mmHg (mean arterial pressure), +57 +/- 11 beats/min (heart rate), -31 +/- 3% (hindquarter resistance), +29 +/- 9% (renal resistance), and +87 +/- 22% (mesenteric resistance), P less than 0.05 compared with saline. The glutamate N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (300 micrograms/kg iv) attenuated the pressor-tachycardic responses to TRH and the pressor-mesenteric constrictor responses to glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Hemodynamics/drug effects , Preoptic Area/physiology , Thyrotropin-Releasing Hormone/pharmacology , Anesthesia , Animals , Dizocilpine Maleate/pharmacology , Glutamates/pharmacology , Glutamic Acid , Injections , Male , Rats , Rats, Inbred Strains , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiology
18.
Dtsch Med Wochenschr ; 121(42): 1292-6, 1996 Oct 18.
Article in German | MEDLINE | ID: mdl-8964203

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A 19-year-old youth was hospitalised because of sudden onset of incomplete lid closure and drooping mouth on the left. He regularly walked through fields and woods; three weeks before admission he had noted swelling and reddening on his neck, which he thought was due to an insect bite. When 9 years old a functional heart murmur and 1 degree AV block (P-R interval 0.25s) had been found. Physical examination showed peripheral facial paresis and a 2/6 systolic murmur over the aortic area. INVESTIGATIONS: As Borreliosis (Lyme disease) was suspected, relevant laboratory tests were performed. These revealed specific IgM antibodies against Borrelia burgdorferi. Polymerase chain reaction demonstrated B. burgdorferi-specific DNA in cerebrospinal fluid and urine. The ECG showed 1 degree AV block (P-R interval 0.28s). TREATMENT AND COURSE: Ceftriaxone was administered at once (4 g, followed by 2 g daily intravenously for 14 days). The P-R interval increased to maximally 0.31 s and transient incomplete right bundle branch block developed on the second day. Long-term ECG monitoring also revealed ventricular arrhythmias (Lown IVb), but they gradually disappeared. The neurological signs regressed completely within five days of the start of treatment, while the P-R interval had returned to its initial value of 0.25 s 3 months later. CONCLUSION: The case makes clear that an ECG should be recorded in borreliosis even in the absence of cardiac symptoms. Hospitalisation with long-term monitoring becomes necessary if it is abnormal.


Subject(s)
Facial Paralysis/etiology , Heart Block/congenital , Heart Block/complications , Heart Murmurs/etiology , Lyme Disease/complications , Adult , Ceftriaxone/administration & dosage , Cephalosporins/administration & dosage , Combined Modality Therapy , Electrocardiography , Facial Paralysis/diagnosis , Facial Paralysis/therapy , Heart Block/diagnosis , Heart Block/therapy , Heart Murmurs/diagnosis , Heart Murmurs/therapy , Humans , Lyme Disease/diagnosis , Lyme Disease/therapy , Male , Pacemaker, Artificial , Remission Induction
19.
Eur Heart J ; 16(12): 1886-91, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8682022

ABSTRACT

Patients with chronic heart failure have an increased ventilation/carbon dioxide production ratio (VE/VCO2) during exercise. Recently it was discussed whether the cause of this increase was a ventilatory stimulus driven other than by CO2. Dyspnoea during exercise is thought to be related to impaired respiratory function. However, clinical confirmation is scarce. Ninety-two patients (age 51 +/- 9 years) with heart failure due to idiopathic dilated cardiomyopathy exercised on a bicycle ergometer to exhaustion, and measurement of ventilatory gases and Swan-Ganz catheterization were performed. The maximal oxygen consumption corrected for body weight (VO2max. kg-1) was 16.6 +/- 5.5 ml x min-1 x kg-1. The increase in (VE/VCO2) during exercise was related to an increase in respiratory rate (r = 0.43; P < 0.00001) but not to an increase in cardiac index or capillary wedge pressure. Nineteen patients stopped exercising because of dyspnoea. Their maximal tidal volume and VO2max . kg-1 were lower than the 67 patients who stopped exercise because of fatigue (P < 0.001 and P < 0.00001 respectively). Other variables showed no significant difference. In conclusion, the increase in VE/VCO2 during exercise may reflect a non-CO2 driven ventilatory stimulus as it cannot be attributed to increased pulmonary vascular pressures or an insufficient increase in cardiac output leading to a ventilation-perfusion mismatch. Low oxygen uptake is a prominent finding in patients with chronic heart failure who experienced dyspnoea during exercise, and dyspnoea is in part related to impaired respiratory function.


Subject(s)
Carbon Dioxide/blood , Dyspnea/etiology , Exercise Test , Heart Failure/physiopathology , Oxygen/blood , Ventilation-Perfusion Ratio/physiology , Adult , Aged , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Dyspnea/physiopathology , Female , Heart Failure/diagnosis , Hemodynamics/physiology , Humans , Male , Middle Aged , Prospective Studies
20.
J Lipid Mediat Cell Signal ; 15(3): 255-84, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9041476

ABSTRACT

Platelet-activating factor (PAF) is a potent phospholipid mediator released from inflammatory cells in response to diverse immunologic and non-immunologic stimuli. Animal studies have implicated PAF as a major mediator involved in coronary artery constriction, modulation of myocardial contractility and the generation of arrhythmias which may bear on cardiac disorders such as ischemia, infarction and sudden cardiac death. PAF effects are induced by direct actions of PAF on cardiac tissue to modify chronotropic and inotropic activity, or indirectly via the release of eicosanoids such as thromboxane A2 (TXA2), leukotrienes (LT) or cytokines (TNF alpha). The development of selective, high affinity PAF receptor antagonists has permitted investigations on the role of PAF in experimental animal models of cardiac injury. In vivo and in vitro studies strongly suggest that PAF receptor antagonists might convey therapeutic benefits in ischemic conditions and certain arrhythmias. In addition, PAF antagonists might have a cardiac allograft-preservation effect. Although clinical studies with PAF receptor antagonists in patients with cardiac diseases have not yet been reported, the experimental results to date suggest that PAF receptor antagonists might be useful in some specific cardiac disorders in humans.


Subject(s)
Heart Diseases/drug therapy , Platelet Activating Factor/metabolism , Platelet Membrane Glycoproteins/antagonists & inhibitors , Receptors, Cell Surface , Receptors, G-Protein-Coupled , Animals , Cells, Cultured , Coronary Vessels/drug effects , Heart/drug effects , Heart Diseases/metabolism , Heart Transplantation , Humans , Molecular Structure , Myocardial Contraction/drug effects , Myocardial Ischemia/metabolism , Myocardium/metabolism , Platelet Activating Factor/antagonists & inhibitors , Platelet Activating Factor/biosynthesis , Platelet Activating Factor/pharmacology
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