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P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 181 records · Page 10Linked to original sources
PubMed1990

Activation of bone marrow-derived mouse macrophages by bacterial lipopeptide: cytokine production, phagocytosis and Ia expression.

The lipopeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-(R)-cysteinyl-a lanyl-glycine (Pam3Cys-Ala-Gly), a synthetic analogue of the N-terminal part of bacterial lipoprotein, induces the secretion of interleukin (IL) 1, IL 6 and tumor necrosis factor (TNF)-alpha in bone marrow-derived macrophages that have been cultured in vitro for up to 20 days. IL 6 and TNF-alpha secretion increased from day 6 to day 20 whereas IL 1 secretion increased until day 13 and decreased on day 20. In contrast to the enhancement of cytokine production, phagocytosis of IgG-coated sheep erythrocytes and Ia expression were found to be diminished after treatment with lipopeptide for 24 h. Morphological studies revealed lipopeptide-induced changes of macrophage cultures. The data presented here show the potential of the lipopeptide as a strong activator of bone marrow-derived macrophages.

Animals↗
PubMed1990

Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors.

In a previous study, prolonged low-frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long-lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5-HT) systems were involved. More recently, we have shown that the 5-HT1 receptors are involved in the post-stimulatory decrease in blood pressure. In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 +/- 10% (P less than 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h. One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post-stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5-HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5-HT1&2 receptor antagonist) abolished the post-stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205-930 (5-HT2 and 5-HT3 blocking agents respectively). In another group of experiments, the serotonin receptor antagonists were administered post-stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1990

Role of different serotonergic receptors in the long-lasting blood pressure depression following muscle stimulation in the spontaneously hypertensive rat.

In a previous study prolonged low-frequency muscle stimulation in the hind leg of the spontaneously hypertensive rat (SHR) was shown to induce a reduction in blood pressure (about 15 mmHg) that lasted for many hours. We showed in that study that endorphin and serotonin systems were involved. In the present study drugs with selective affinity for the serotonin (5-HT) receptors were used to analyse further the involvement of different serotonin systems. In one group of SHR, a prestimulatory dose of metitepine maleate (a 5-HT1 and 5-HT2 receptor antagonist) completely abolished the post-stimulatory depressor response. The long-lasting depressor response was still present, although less pronounced, after a bolus dose of the 5-HT2 blocking agent ritanserin (R 55667) at the start of stimulation. The 5-HT3 receptor antagonist ICS 205-930 did not influence the response at all, nor did the selective 5-HT1a receptor agonist 8-OH-DPAT enhance the depressor response. These results indicate that the reduction in blood pressure after muscle stimulation is mainly mediated by the 5-HT1 receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Role of opioid receptors in the long-lasting blood pressure depression after electric muscle stimulation in the hind leg of the rat.

In a previous study, electrically induced contractions of the gastrocnemius muscle in conscious spontaneously hypertensive rats were shown to induce a blood pressure reduction of 15-20 mmHg lasting several hours. We showed in that study that endogenous opioid systems were involved. In this study, drugs with selective affinity for different opioid receptors were used to analyse further the involvement of endogenous opioid systems in the post-stimulatory drop in blood pressure in spontaneously hypertensive rats. Prestimulatory intracerebroventricular administration of beta-FNA (a mu-receptor antagonist) did not significantly influence the response at all, nor did a lower intravenous dose of naloxone reverse the post-stimulatory drop in blood pressure. High-dose naloxone (15 mg kg-1) increased post-stimulatory blood pressure by around 10 mmHg. About 50% of the drop thus remained after this treatment. A similar, partial reversal of the decreased blood pressure was seen after intravenous administration of a delta-receptor antagonist, ICI 154,129. However, the depressor response was completely reversed by a low intravenous dose of MR 2266 BS (a kappa-receptor antagonist). These results suggest that the reduction in blood pressure after muscle stimulation is mainly mediated by the opioid kappa-receptor. A certain involvement of the delta-receptor is also indicated.

Animals↗
PubMed1990

The effects of mu, delta- and kappa-opioid receptor antagonists on the pain threshold increase following muscle stimulation in the rat.

In a previous study, prolonged low-frequency muscle stimulation, inducing dynamic contractions in the hind leg of unanaesthetized rats, was shown to give rise to a hypoalgesia. The increase in pain threshold, measured as squeak threshold to noxious electric pulses, lasted 3 h. In the present study, the involvement of the endogenous opioid system in the post-stimulatory analgesia was investigated using selective opioid receptor antagonists. The post-stimulatory analgesia was completely reversed back to prestimulatory control levels by naloxone, 1 mg kg-1. ICI 154,129 and MR 2266 BS, selective delta- and kappa-receptor antagonists respectively, did not significantly influence the post-stimulatory analgesia, although ICI 154,129 had a minor pain threshold-lowering effect. Rats pretreated with beta-funaltrexamine, a mu-receptor antagonist, did not exhibit any post-stimulatory analgesia. These results suggest that opioid systems are involved in the increase in pain threshold after muscle stimulation and that the analgesic response is both elicited and maintained by the mu-receptor.

Analgesia↗
PubMed1990

Electric muscle stimulation in the spontaneously hypertensive rat induces a post-stimulatory reduction in activity: role of different opioid receptors.

We have previously shown that prolonged low-frequency muscle stimulation, inducing contractions of the gastrocnemius muscle, in conscious spontaneously hypertensive rats leads to an opioid-mediated post-stimulatory reduction in blood pressure and analgesia. In the present study we investigated whether muscle stimulation would also induce a post-stimulatory reduction in behavioural activity in the spontaneously hypertensive rats. Selective opioid receptor antagonists were used to analyse the involvement of endogenous opioids. Muscle stimulation, lasting 60 min, induced a post-stimulatory sedation that outlasted the stimulation for hours. Sniffing, locomotor activity and total behavioural activity were significantly reduced. The post-stimulatory reduction in activity was reversed back to control levels by a high dose of naloxone (15 mg kg-1 i.v.). The selective mu-receptor antagonist beta-funaltrexamine, given intracerebroventricularly before stimulation, did not influence the development of the post-stimulatory drop in activity. The delta-receptor antagonist ICI 154,129 had no effect at all on the already developed sedation, whereas MR 2266 BS, a kappa-receptor antagonist (3 mg kg-1 i.v.), completely reversed the drop in activity. These results show that muscle stimulation gives rise to an opioid-mediated post-stimulatory reduction in activity in spontaneously hypertensive rats. The results also indicate the involvement of the opioid kappa-receptor in the behavioural response.

Animals↗
PubMed1990

Synthetic peptide segments from the Escherichia coli porin OmpF constitute leukocyte activators.

After characterization of the porin OmpF and selection of molecular structures responsible for leukocyte activation by using computer-assisted epitope analysis, the analogs OmpF (153-174) (containing amino acids 153 to 174), OmpF (157-174), and OmpF (275-285) were synthesized and tested. Like the native protein, the segments were mitogenic for BALB/c splenocytes and induced B lymphocyte differentiation into antibody-producing plasma cells and tumor cytotoxicity of macrophages against the fibroblast cell line L929. We thus demonstrated that defined peptide segments are responsible for the leukocyte-activating properties of a major bacterial surface protein.

Animals↗
PubMed1990

Preparation of human and murine monoclonal antibodies: antigens combined with or conjugated to lipopeptides constitute potent immunogens for in vitro and in vivo immunizations.

Lipopeptide analogues of bacterial lipoprotein constitute polyclonal B lymphocyte activators. Combined with or covalently coupled to antigens, they act as potent adjuvants. We could show that antigens (BSA-DNP, TNP-SRBC, saxitoxin, HIV-1 gp160(BH10303-329, EGFR516-523) combined with or coupled to the synthetic lipodipeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-(R)-cysteinyl-s erine (P3CS) constitute active immunogens in vivo in mice. They were also able to induce an in vitro humoral immune response in the murine and human systems, and B lymphocytes thus activated were suitable for fusion. Thus, the antigens chaperonin/phytochrome, BSA-saxitoxin, histamine, HIV-1 gp160 (BH10(303-329)), HIV-1 gp160 (RF316-341)), and HIV-2 p17 (ROD111-121) combined with or conjugated to P3CS could be used for in vitro immunization followed by the preparation of murine and human monoclonal antibodies. Our novel immunization procedure offers reproducibility, high antibody titers often after one immunization, lack of toxicity of the adjuvants, easy chemical preparation of the conjugates in mg amounts, and the applicability of the conjugates for screening for the antibodies obtained.

Adjuvants, Immunologic↗
PubMed1990

Endorphins and exercise: physiological mechanisms and clinical implications.

In this paper we discuss recent experimental and clinical findings which lead us to propose that prolonged rhythmic exercise can activate central opioid systems by triggering increased discharge from mechanosensitive afferent nerve fibers (Group III or A-delta) arising from contracting skeletal muscle. We review evidence that supports the concept that many of the cardiovascular, analgesic, and behavioral effects of exercise are mediated by this mechanism and that the same or similar mechanisms are responsible for the central and peripheral effects of acupuncture. Based on this hypothesis, and supporting evidence from human and animal studies, we suggest a mechanism and a potential therapeutic role for exercise in the treatment of selected patients with disorders as diverse as hypertension, addiction, depression, and anorexia nervosa.

Acupuncture Therapy↗
PubMed1990

[Learning from mistakes. Thoughts on preclinical care of accident victims based on 10-year experience in a large city of West Germany].

On the occasion of the 25th anniversary of preclinical emergency medicine a review of the last decade of preclinical treatment of polytraumatized patients was performed. Initially preclinical emergency medical services were established for the immediate care of victims in road accidents. Therefore these services were first usually stationed in Centers for Surgery or Traumatology. Emergency physicians in these were inevitably well trained in the emergency treatment of trauma patients. The Achilles tendon then was their limited ability to cope with differentiated internal problems. Whereas the quality of preclinical treatment in non-traumatic emergencies gradually increased during the last 10 years due to compulsory postgraduate training courses and due to the fact, that the percentage of physicians and anesthetists among the emergency crews also gradually increased, the average emergency physician no longer possessed enough practical experience with the early treatment of trauma patients, a disadvantage, which could not be sufficiently compensated in compulsory postgraduate training courses. This could be demonstrated in our 10 year quality control. Only physicians of Search and Rescue helicopter teams and residents of surgical and trauma departments made significantly few mistakes in the early treatment of polytraumatized patients. Typical mistakes of less experienced physicians could be sorted into 5 groups: --volume treatment: incorrect estimation of the severity of polytrauma/incorrect estimation of the amount of blood loss/insufficient substitution of volume/logistical mistakes. --O2 treatment: incorrect estimation of the degree of blunt thoracic trauma/hesitant indication for early artificial respiration/hesitant indication for thoracic drainage. --local treatment: incorrect estimation of the severity of soft tissue trauma/incorrect treatment of amputated limbs. --logistics and transport: additional iatrogenic laceration of soft tissues due to insufficient reposition and retention/logistical mistakes in choosing in the best means of transport and the best suited hospital for the patient. --special types of trauma: incorrect estimation of the severity of burn trauma/lack of experience in triage in cases of major accidents. To get better results in the early treatment of polytraumatized patients, the installation of a specialized emergency medical service for trauma patients in the main trauma centers of major cities combined with the function of the surgeon in charge for major accidents and catastrophies is to be discussed.

Diagnostic Errors↗
PubMed1990

Subacute carbon disulfide exposure modifies adrenergic cardiovascular actions in rats.

The influence of subacute carbon disulfide exposure (1.66 or 3.32 mmol/kg) on cardiovascular actions of epinephrine (1 or 4 micrograms/kg iv) and norepinephrine (2 or 10 micrograms/kg iv) was investigated in the urethane-anesthetized rat model. Hypertensive adrenergic effects were enhanced and inotropic effects were diminished in carbon disulfide exposed rats. Atrioventricular impulse conduction was delayed after carbon disulfide exposure, and we observed an increased number of extrasystoles in these animals. Transient T-wave elevation after catecholamine injection was augmented in carbon disulfide exposed rats. Our results demonstrate that subacute carbon disulfide exposure modifies adrenergic cardiovascular actions in rats.

Animals↗
PubMed1990

Effects of carbon disulfide on cardiovascular function after acute and subacute exposure of rats.

Epidemiologic studies provided evidence that increased heart disease mortality after carbon disulfide exposure is not only related to carbon disulfide-caused coronary sclerosis but they suggest that there would be reversible, direct cardiotoxic effects. In order to investigate such direct toxic effects of carbon disulfide on the cardiovascular system, in this study carbon disulfide was administered acutely and subacutely to rats. Blood pressure and heart rate in normotensive conscious unrestrained rats were not markedly influenced by both acute and subacute carbon disulfide administration. Depressant effects of carbon disulfide administration on intracardiac impulse generation and conduction as well as on contractile force were observed in urethane-anesthetized rats. The appearance of several forms of aconitine-induced arrhythmias was delayed after subacute treatment with carbon disulfide. In the coronary occlusion model, subacute carbon disulfide treatment reduced the survival rate accompanied by marked influences on arrhythmia development. Our results show that short term carbon disulfide exposure alters cardiac function in rats under physiological and pathophysiological conditions.

Aconitine↗
PubMed1989

Light- and electron-microscopic investigation of the rat subcommissural organ grafted under the kidney capsule, with particular reference to immunocytochemistry and lectin histochemistry.

There is increasing evidence that, in the rat, a serotonin-mediated neural input may have an inhibitory influence on the secretory activity of the subcommissural organ (SCO). In the present investigation the rat SCO was studied 7, 30 and 90 days after transplantation under the kidney capsule, an area devoid of local serotonin-containing nerves. The grafted tissue was examined by use of immunocytochemistry employing a series of primary antisera, lectin histochemistry and transmission electron microscopy. The grafted SCO survived transplantation and contained, in addition to secretory ependymal and hypendymal SCO-cells, also elements immunoreactive with antisera against glial fibrillary acidic protein or S-100 protein. In transplants, SCO-cells produced a material displaying the characteristic immunocytochemical and lectin-binding properties of SCO-cells observed under in-situ conditions. The ependymal cells lined 1-3 small cavities, which contained secretory material. A fully developed structural equivalent of Reissner's fiber was, however, never found. The immunocytochemical and ultrastructural study of the grafted SCO showed an absence of nerve fibers within the graft and suggested a state of enhanced secretory activity. A network of protruding basal lamina structures connected the secretory cells to the newly formed capillaries revascularizing the SCO. One week after transplantation, long-spacing collagen started to appear in expanded areas of such laminar networks and also in the perivascular space. It is suggested (i) that the formation of long-spacing forms of collagen is triggered by factors provided by the SCO-secretory cells, and (ii) that secretory material of the ependymal and hypendymal cells may reach the reticular extensions of the basal lamina. In contrast to the SCO in situ, the grafted SCO-cells showed a positive immunoreaction for neuron-specific enolase. They became surrounded by a S-100-immunoreactive glial sheath that separated them from other transplanted cell types and the adjacent kidney tissue of the host.

Animals↗
PubMed1989

Induction of tumor cytotoxicity in murine bone marrow-derived macrophages by two synthetic lipopeptide analogues.

Lipoprotein from the outer membrane of Escherichia coli and the synthetically prepared lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 derived from the N-terminus of lipoprotein constitute potent macrophage and polyclonal B-lymphocyte activators. The compounds have also been shown to induce tumor cytotoxicity in murine bone marrow-derived macrophages (BMDM). Bone marrow stem cells were cultured in the presence of colony-stimulating factor 1 to yield BMDM of 98 to 99% purity at day 8. After stimulation with the lipopeptides on days 4, 6, 8 and 10 of bone marrow culture, the cytotoxic effect of BMDM on the tumor cell line L929 was determined in a [3H]thymidine release assay. Maximum tumor cytotoxicity was found on day 8 with an optimal effector/target-cell ratio of 10:1, and a duration of lipopeptide stimulation of 4 h. The supernatants of lipopeptide stimulated BMDM also showed cytotoxic activity that could be inhibited by antiserum against tumor necrosis factor alpha. The effects of the lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 were comparable or superior to those exerted by lipopolysaccharide. Our results demonstrate that synthetic lipopeptides are potent activators for murine BMDM and may therefore prove to be an important tool for the elucidation of the role of macrophages in the host defence mechanisms against tumor cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

[Short term effects of carbon disulfide on the intracardial irritation development and transmission in the rat].

Studies were conducted into effects of acute and subacute CS2 application on intracardiac irritability and conduction in rat. Aconitine-induced arrhythmia and the coronary occlusion method were used as pathophysiological models. Under physiological conditions, short-time exposure to CS2 caused deceleration of intracardiac impulse conduction, while under pathophysiological conditions, modified arrhythmia or reduced survival rate was the result.

Animals↗