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Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 109 records · Page 6Linked to original sources
PubMed1997

V2 receptor antagonism of DDAVP-induced release of hemostasis factors in conscious dogs.

The synthetic arginine vasopressin (AVP) analog 1-desamino-8-D-arginine vasopressin (DDAVP) is used in a variety of hemorrhagic disorders. The present experiments were designed to further characterize the mechanism of DDAVP-induced release of hemostasis factors. The [3H]AVP-labeled AVP receptor in canine renomedullary membranes exhibited an AVP V2 profile because the V2 receptor agonist DDAVP displayed similar subnanomolar affinities as the natural hormone AVP, whereas the two selective V1a compounds SR 49059 and d(CH2)5Tyr(Me)AVP as well as the selective V1b agonist D-Pal and oxytocin were much less potent. The rank order of the binding affinities of three V2 receptor antagonists was SR 121463 (a newly described selective V2 receptor antagonist) > OPC 31260 >> d(CH2)5D-Ile2,Ile4AVP. In conscious dogs, DDAVP (0.1-1 microg/kg I.V.) caused a dose-related increase (maximum, 43-52% at 30 min) in plasma levels of factor VIII (FVIII), von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA), but not in levels of plasminogen activator inhibitor-1. A DDAVP-induced hemostasis factor release was also observed in bilaterally nephrectomized dogs. Pretreatment with SR 121463 inhibited DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels in a dose-dependent manner (ID50 = 14.0 +/- 4.0, 12.4 +/- 3.0 and 16.7 +/- 1.0 microg/kg I.V., respectively). OPC 31260 (300 microg/kg I.V.) revealed a lower activity than SR 121463, and d(CH2)5[D-Ile2,Ile4]AVP (30 microg/kg I.V.) was without effect on the DDAVP response. Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels. The present results, therefore, strongly suggest that the effect of DDAVP on hemostasis factors occurs via a specific interaction with extrarenal V2 receptors.

Animals↗
PubMed1997

[Treatment of ureteral stenosis using high pressure dilatation catheters].

INTRODUCTION: High-pressure dilatation catheters have been proposed as an alternative to open surgery in the treatment of ureteric strictures because of the low morbidity and short hospital stay. The objective of this study was to evaluate the results of this technique in patients with inflammatory ureteric strictures or uretero-ileal strictures. METHODS: From April 1991 to September 1996, 25 strictures were treated by antegrade or retrograde dilatation with a high-pressure balloon catheter followed by stenting with a double J stent for an average of 2.1 months (1-5): 14 uretero-ileal strictures (tuberculosis, schistosomiasis, iatrogenic, radiotherapy). A good immediate result was defined as intraoperative rupture of the stricture under fluoroscopic control. A good long-term result was defined as absence of recurrence of the stricture, evaluated clinically and radiologically (IVU and/or ultrasonography). RESULTS: The good immediate result rate was 82% (19 out of 23 strictures, with 2 non-evaluable cases). One intraoperative complication was observed (double J stent advanced too for into the ureter). 22 strictures were evaluable after removal of the double J stent and the good long-term result rate was 64% with a mean follow-up of 8.5 months (0.3-24). 8 patients developed a recurrence: 4 after Bricker, 3 with inflammatory strictures after radiotherapy and J with peritoneal carcinomatosis. CONCLUSION: This study shows that high-pressure balloon catheter dilatation of non-neoplastic ureteric strictures provides good results and can be considered to be the first-line treatment for these lesions.

Adult↗
PubMed1997

Bacterial lipopeptides constitute efficient novel immunogens and adjuvants in parenteral and oral immunization.

Synthetic lipopeptide analogues derived from the N-terminus of bacterial lipoprotein constitute potent B-lymphocyte and macrophage/monocyte activators in vitro. In vivo they act as immunoadjuvants in parenteral and oral immunization when administered in combination with antigens. When added to bacterial or viral vaccines, lipopeptides markedly enhance the vaccine effect. After the coupling of lipopeptides to haptens or non immunogenic low molecular mass antigens, a specific antibody response is induced often after only one application of the conjugate. The response can be further enhanced by introducing haplotype specific T helper cell epitopes into the conjugate. Lipopeptide antigen conjugates can also be applied as synthetic vaccines that give protection e.g. against foot-and-mouth-disease. The novel chemically well defined lipopeptides described here can be synthesized in gram amounts with high purity and reproducibility; they are non-toxic and can be stored for long time even at room temperature. For veterinary application, by replacing Freund's adjuvant, side reactions and inflammatory processes are avoided.

Adjuvants, Immunologic↗
PubMed1997

Physical exercise, endogenous opioids and immune function.

The experimental data available today strongly indicate that various types of physiological stressors, including physical exercise and emotional stress, can influence immune function. Natural immunity represents a first line of defence in viral infections and cytotoxicity to a variety of tumour cells. Natural immunity is strongly influenced by chronic exercise and this regulation includes interaction between the nervous, endocrine and immune systems. Central mechanisms including the endogenous opioids are of great interest. Chronic activation of endogenous opioid systems augments natural cytotoxicity and the possible involvement the opioids in the exercise-induced enhancement of natural immunity is discussed. Also, catecholamines seem to play an important role in the regulation of immune function, both after chronic exercise and emotional stress. The physiological significance of the reported changes in natural cytotoxicity after exercise-training is as yet unclear.

Animals↗
PubMed1996

Murine bone marrow-derived macrophages constitute feeder cells for human B cell hybridomas.

Murine bone marrow-derived macrophages (BMDM), a homogeneous cell population easily obtainable in large quantities and at reproducible quality by in vitro differentiation, were used as feeder cells for human B cell hybridomas after fusion or during recloning. We used as antigens for the in vitro immunization of human B lymphocytes from peripheral blood as well as from tonsils: (i) synthetic peptides representing immunogenic sequences of gp160 and Nef of HIV-1, coupled to the lipopeptide carrier N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2 RS)-propyl]-(R)-cysteinyl(-seryl-seryl) (P3 CSS-[gp160(303-329)] and P3C-nef24), (ii) the toxins saxitoxin and microcystin, coupled to BSA (BSA-STX and BSA-MCYST). After fusion with the mouse-human heteromyeloma CB-F7, we could demonstrate that BMDM exert a strong growth supporting effect on post-fusion cultures, resulting in 81.6% versus 23.6% growth-positive wells for P3C-nef24, and 100% versus 71.2% growth-positive wells for BSA-STX stimulated cells in cultures with and without BMDM, respectively. Furthermore, clones in wells with BMDM grew much more rapidly, resulting in 24.3% versus 3.6%, 98.1% versus 42.2% and 56.7% versus 6.7% of cultures ready for screening 2 weeks after fusion of P3C-nef24, P3CSS-[gp160(303-329)], and BSA-STX stimulated lymphocytes, respectively. Apart from their effect on cell growth, murine BMDM also increased the percentage of immunoglobulin (Ig)-producing cultures after fusion, as shown for BSA-STX stimulated lymphocytes (47.8% versus 6.7%), as well as the percentage of cultures producing specific antibodies, as demonstrated with BSA-MCYST activated cells (42% versus 10%). Finally, recloning efficiencies of two human B cell hybridomas (E 10 and F 2) were raised profoundly by BMDM, resulting in 100% versus 64.2% and 90.9% versus 44.2% growth-positive wells after recloning on a ten cells/well level. As murine BMDM can also be stored in liquid nitrogen without loss of activity, they constitute ideal feeder cells for the establishment of human B cell hybridomas.

Amino Acid Sequence↗
PubMed1996

Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats.

We have studied the effect of chronic intracerebroventricular (i.c.v.) infusion of different opioid peptides on natural killer (NK) cell mediated cytotoxicity in vivo in the spontaneously hypertensive rat (SHR). The in vivo NK cell activity was measured as the clearance of 51Cr-labelled YAC-l lymphoma cells from the lung tissues. Further, the phenotype of lymphocytes in spleen and peripheral blood was analysed by flow cytometry (FACS). All opioid drugs were administered i.c.v. for 6 days with osmotic minipumps releasing 1.0 microliter/h. beta-Endorphin (10 or 20 micrograms/rat per day) significantly increased NK cell cytotoxicity in vivo. The opioid receptor antagonist naloxone (10 mg/kg, i.p.) given immediately before the injection of YAC-lymphoma cells, completely abolished the effects of i.c.v. administered beta-endorphin. Corresponding doses of beta-endorphin administered subcutaneously (s.c.) with minipumps for 6 days did not significantly affect NK cell cytotoxicity. Neither Leu- or Met-enkephalin (20 micrograms/rat per day) nor dynorphin (20 micrograms/rat per day) administered i.c.v. had any significant effects on NK cell activity. In beta-endorphin treated SHR, the percentage of cells with NK cell phenotype (OX52+/CD5-) in peripheral blood was not significantly different from that of controls, while the percentage of cells with T cell phenotype (CD5+/OX52-) was significantly decreased. The percentage of splenic NK cells (OX52+/CD5-) and T cells (CD5+/OX52-) was also unchanged by beta-endorphin treatment i.c.v. These results suggest that of the opioid peptides administered i.c.v., only beta-endorphin augments in vivo NK cell mediated cytotoxicity. We thus conclude that these effects most probably are centrally and opioid receptor mediated effects, since beta-endorphin in the same dose administered peripherally does not influence in vivo NK cell cytotoxicity.

Administration, Cutaneous↗
PubMed1996

Induction of the WAF1/CIP1 protein and apoptosis in human T-cell leukemia virus type I-transformed lymphocytes after treatment with adriamycin by using a p53-independent pathway.

The WAF1/CIP1 protein has been identified as a downstream mediator of the tumor suppressor p53 in regulating cell cycle progression through a G1-phase check-point. Recent work has implicated the functional status of p53 as a critical determinant in the apoptotic response of certain cell lines to DNA damaging agents. By using human T-cell leukemia virus type I-transformed lymphoid cell lines that differ in their level and function of wild-type p53, we investigated the induction of WAF1/CIP1 and apoptosis after exposure to Adriamycin, a genotoxic agent. We found that regardless of the p53 status in these cell lines, WAF1/CIP1 RNA was rapidly induced in response to Adriamycin treatment. An elevated level of WAF1/CIP1 protein was observed as well. Additionally, we demonstrated that apoptosis was induced in all cell lines analyzed despite some having functionally inactive p53 protein. Our data suggest that a p53-independent pathway may play a role in the apoptotic response observed in some cell lines after exposure to DNA damaging agents.

Antibiotics, Antineoplastic↗
PubMed1996

Calcium dynamics in cardiac myocytes as a target of dichloromethane cardiotoxicity.

The purpose of the present study was to determine if cardiac actions of dichloromethane (DCM) in vivo correlate with in vitro alterations of Ca2+ dynamics in cardiac myocytes. Neonatal rat ventricular myocytes were obtained from 2- to 4-day-old rats, and electrically induced fluctuations of cytosolic free Ca2+ concentration ([Ca2+]i) in single cardiomyocytes were investigated using spectrofluorometric analysis of fura-2-[Ca2+]i binding. In cultured myocytes, cumulative exposure to 0.64-40.96 mM DCM resulted in a concentration-dependent and reversible decrease in the magnitude of [Ca2+]i transients with IC10 and IC50 values of 7.98 and 18.82 mM, respectively. Total inhibition of [Ca2+]i transients and cessation of beating were observed at 40.96 mM DCM. Suffusion with DCM for 40 min did not cause morphological alterations of the myocytes. In a urethane-anesthetized rat model, left ventricular pressure was measured by introducing a tip catheter via the carotid artery into the left ventricle, the ECG was recorded by two needle electrodes applied subcutaneously to the chest wall, and arterial pressure was measured via the femoral artery. Oral administration of 3.1-12.4 mmol DCM/kg resulted in DCM blood concentrations between 1.0 and 1.6 mM, accompanied by a dose-dependent decrease in contractile force and heart rate without influencing blood pressure and ECG tracings. Moreover, DCM treatment provided significant protection against arrhythmia development due to CaCl2-infusion. In spite of the slight discrepancy between DCM blood concentrations and in vitro concentrations of DCM for [Ca2+]i transient inhibition, present data are consistent with the view that cardiac effects after DCM exposure are mediated by alterations of Ca2+ dynamics during excitation-contraction coupling.

Anesthesia↗
PubMed1996

Natural immunity and chronic exercise in rats. The involvement of the spleen and the splenic nerves.

We have previously shown that voluntary running for 4-5 weeks in the spontaneously hypertensive rat (SHR) significantly increased in natural cytotoxic mechanism in vivo, measured as clearance of 51Cr YAC-1 lymphoma cells from the lungs. In the present study, we have studied the possible role of the spleen and the splenic nerves in this augmentation. The SHR were randomly allocated to either a voluntary exercise group or a sedentary control group. After four weeks of exercise the runners and sedentary control SHR were further assigned to one of four groups: 1) no surgery, 2) sham operation, 3) splenic nerve section and 4) splenectomy. Splenectomy drastically reduced in vivo cytotoxicity in both runners and sedentary controls, but in vivo cytotoxicity of splenectomized voluntary runners was significantly higher than that of splenectomized sedentary control animals. Selective denervation of the spleen did not affect the in vivo cytotoxicity. These results indicate that the enhanced in vivo natural cytotoxic mechanism following voluntary chronic exercise in SHR is partly dependent on intact splenic function. However, this enhancement does not seem to be mediated by the splenic sympathetic nerves.

Animals↗
PubMed1996

Synthetic peptides coupled to the lipotripeptide P3CSS induce in vivo B and Thelper cell responses to HIV-1 reverse transcriptase.

To evaluate the ability of the lipotripeptide P3CSS to increase peptide-specific immune responses in vivo, we immunized mice from different inbred strains (BALB/c, C3H/HeJ, C57BL/6) with the 22-mer lipopeptide conjugates P3CSS-[RT-(522-543)] and P3CSS-[RT-(528-549)] of HIV-1 reverse transcriptase (RT) which included an immunodominant Th epitope [i.e. RT-(528-543)] characterized previously. Analysis of T and B cell responses to these lipopeptide conjugates indicated that specific Th responses could be readily induced in vivo. The peptide segments could also efficiently prime mice for secondary recognition of native RT. The use of shorter peptides permitted a delineation of the minimal T cell recognition site of this RT C-terminal region [i.e. RT-(528-540)]. Close to this T cell epitope we identified a B cell determinant containing the motif EQVD [RT-(546-549)] which was recognized in three different strains of mice (H-2b, H-2d and H-2k). A comparison with X-ray analysis of the C-terminal region of HIV-1 reverse transcriptase indicated exposed positions of these Th and B cell epitopes. Both the presence of T and B cell sites and its limited polymorphism make the region RT-(528-549) a promising candidate for vaccine design. The use of the P3CSS adjuvant/carrier principle as a nontoxic adjuvant may be of major importance in the development of vaccines applicable to humans.

Adjuvants, Immunologic↗
PubMed1996

Acute mental stress but not enforced muscle activity transiently increases natural cytotoxicity in spontaneously hypertensive rats.

The influence of acute mental stress and the effect of electrically induced skeletal muscle contractions on natural cytotoxicity in vivo was investigated in spontaneously hypertensive rats Natural cytotoxicity in vivo was measured as the clearance of injected 51Cr-labelled YAC-1 lymphoma cells from the lungs, which are specifically lysed by natural killer cells. The mental stress consisted of an air jet directed towards the animals in their cage for 25 min. During the mental stress there was a significant increase in natural cytotoxicity. Thus, retained radioactivity in the lungs was decreased to 74 +/- 6% of the control levels which was set to 100% (P < 0.01). This augmentation of YAC-1-cell clearance could be blocked with the beta-adrenergic receptor antagonist Timolol. Two hours after termination of the air stress, in vivo cytotoxicity had returned to control levels. In contrast, acute physical stress, consisting of electrically induced muscle contractions for 60 min, had no significant effects on in vivo cytotoxicity, either during the stimulation or 1, 2 or 24 h after the stimulation. Further, significantly increased plasma levels of adrenaline were seen after the air jet stress, but not after muscle stimulation. There were no significant changes in plasma noradrenaline levels either after air stress or muscle stimulation. These results indicate that changes in in vivo cytotoxicity after mild mental stress are dependent on increased plasma catecholamine levels while acute physical stress without changes in catecholamine levels, does not influence in vivo cytotoxicity.

Animals↗
PubMed1996

Keratinocyte growth factor ameliorates mucosal injury in an experimental model of colitis in rats.

BACKGROUND & AIMS: Keratinocyte growth factor (KGF) is known to enhance tissue repair in the skin; however, its role in the gastrointestinal tract is largely unknown. The aim of this study was to evaluate the effects of exogenous KGF in an experimental model of colitis in rats. METHODS: KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol. In the first two study groups, KGF (5 mg/kg) was administered intraperitoneally 24 hours and 1 hour before induction of colitis; animals were killed 8 hours (n=10) and 1 week (n=10) after injury. In subsequent study groups, KGF or vehicle treatment was begun 24 hours after the induction of colitis at doses of 5 (n=20), 1 (n=10), and 0.1 (n=10) mg/kg intraperitoneally and continued once daily for 1 week. Colonic tissue samples were evaluated macroscopically and microscopically for mucosal injury and assayed for myeloperoxidase activity. RESULTS: Administration of KGF after but not before induction of colitis significantly ameliorated tissue damage. Macroscopic necrosis and microscopic ulcerations were reduced by 40%-50% at KGF doses of 1 and 5 mg/kg. CONCLUSIONS: Exogenous KGF has a key role in mucosal healing in an experimental model of colitis in rats.

Animals↗
PubMed1996

Degradation of the fluoroquinolone enrofloxacin by wood-rotting fungi.

The veterinary fluoroquinolone enrofloxacin was degraded in vitro by four species of wood-rotting fungi growing on wetted wheat straw containing carbonyl-14C-labeled drug. A maximum 14CO2 production of 17% per week was observed with the brown rot fungus Gloeophyllum striatum, resulting in up to 53% after 8 weeks. However, rates reached at most 0.2 and 0.9% per week, if enrofloxacin was preadsorbed to native or gamma ray-sterilized soil, respectively.

Adsorption↗
PubMed1996

Voluntary chronic exercise augments in vivo natural immunity in rats.

The effect of chronic voluntary exercise on the immune response was studied in spontaneously hypertensive rats. Exercise consisted of voluntary running in wheels for 5 wk, and the mean running distance was 4.2 km/24 h. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. The clearance of YAC-1 cells in vivo was significantly increased in runners compared with sedentary controls (P < 0.001). The total number of mononuclear cells in the spleen was significantly decreased in runners compared with controls. Analysis of splenic lymphocyte phenotypes revealed a significantly increased fraction of OX52+/CD5- natural killer cells in runners compared with sedentary controls. In contrast to changes in natural immunity, immunoglobulins G and M levels in serum, the antibody response to antigen in vivo, and the proliferation of splenic T cells in vitro were unchanged. Our data suggest that chronic voluntary exercise augments natural cytotoxicity mechanisms in vivo, whereas splenic T-cell proliferation and the antibody-mediated immune response remain unchanged.

Animals↗
PubMed1996

Antagonism of SR 90107A/Org 31540-induced bleeding by protamine sulfate in rats and mice.

The neutralization by protamine sulfate of bleeding enhancement induced by the potent anti-factor Xa pentasaccharide SR 90107A/Org 31540 and by heparin has been studied in rats and mice. Bleeding, as measured by transection of the tail of anaesthetised rats or mice, was increased following the administration of heparin and very high doses of SR 90107A/Org 31540. In rats, i.v. doses of 0.6 mg/kg heparin or 15 mg/kg SR 90107A/Org 31540 were required to enhance bleeding time to approximately the same extent (5- or 7-fold increase), whereas in mice a 13-fold increase in blood loss was observed with i.v. doses of 3 mg/kg heparin or 10 mg/kg SR 90107A/Org 31540. Protamine sulfate (10 mg/kg i.v.) reduced bleeding in rats and mice induced by both compounds. It also neutralized the anti-factor Xa activity as well as the antithrombotic activity of heparin as observed in venous thrombosis models in both species. However, protamine sulfate neither affected the anti-factor Xa activity nor the antithrombotic activity of SR 90107A/Org 31540 in rats and mice. The present results suggest that protamine sulfate may be regarded as a potential antidote to neutralize bleeding side-effects in cases of SR 90107A/Org 31540 overdosing.

Animals↗
PubMed1996

[Thionitrites as potent donors of nitric oxide: example of S-nitroso- and S,S'-dinitroso-dihydrolipoic acids].

Until recently, nitric oxide (NO.) was considered as a toxic radical, but it appears now as an essential messenger implicated in a wide range of biological processes, including immune system, cardiovascular system, and nervous system. An aspect of NO. metabolism in vivo is the formation of a variety of high and low molecular weight nitrosothiols. S-nitrosocysteine and S-nitrosoglutathione are among the biologically derived S-nitrosothiols that are postulated to be carriers of NO.. Although most of the S-nitrosothiols are unstable and spontaneously break down to produce NO. and a disulfide, some of them, including protein thiols, can show significant stability. These molecules are able to convey nitric oxide, that is, to keep, to carry, and then to generate NO. in physiological media, and might display pharmacological effects as potential vasodilators or neuroprotectors. Here, we present the development of new thionitrites R-S-NO having intrinsic antioxidant properties. We report the preparation, the characterization, and the stability studies in aqueous solutions of S-nitroso derivatives of dihydro-alpha-lipoic acid, known for its antioxidant properties.

Antioxidants↗
PubMed1996

[Post-treatment PSA, indicator of radical treatment effectiveness of localized cancer of the prostate].

Prostate specific antigen (PSA) has become essential to the follow-up of radical treatment for T1-T2 tumours. Various assays are available, but require a correlation coefficient to homogenize their results. PSA is probably the most reliable marker for the follow-up of radical prostatectomy (RP), as this operation should make PSA undetectable after 3 weeks. Highly sensitive tests, with a limit of detection of 0.1 ng/ml, allow the earlier laboratory detection of tumour escape (20 to 45%). Anastomotic biopsies are positive in 35 to 50% of cases. Seminal vesicle invasion and positive resection margins are more frequently associated with recurrence. The doubling time and rate of progression of PSA after RP can be used to distinguish local recurrence from metastasis. Urinary PSA is not useful in the follow-up of RP, as it is secreted by the periurethral glands. The use of the PSA after radical radiotherapy is less clearly established, as this treatment is not designed to eliminate all prostatic tissue or render PSA undetectable. Therapeutic efficacy is situated between 1 and 1.5 ng/ml according to the tests and is achieved in approximately 40% of cases after 4 years. A PSA level greater than 3 ng/ml at 3 months is indicative of a poor prognosis. Prospects for the future include the use of highly sensitive assays and reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating prostatic cells. The use of PSA has led to a re-evaluation of the efficacy of radical treatments and could influence the indications for adjuvant treatments.

Forecasting↗