@article{AdeyemoShapiraTombaccinietal.1991,
  author    = {Adeyemo, O. M. and Shapira, S. and Tombaccini, D. and Pollard, H. and Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63087},
  year      = {1991},
  abstract  = {A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{ShuaibXuCrainetal.1990,
  author    = {Shuaib, A. and Xu, K. and Crain, B. and Sir{\´e}n, Anna-Leena and Feuerstein, Giora and Hallenbeck, J. and Davis, JN},
  title     = {Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47433},
  year      = {1990},
  abstract  = {We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments.},
  subject      = {Neurophysiologie},
  language  = {en}
}
@article{AdeyemoSiren1992,
  author    = {Adeyemo, M. and Sir{\´e}n, Anna-Leena},
  title     = {Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (±)- anatoxin-a},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63027},
  year      = {1992},
  abstract  = {0. M. ADEYEMO and A.-L. SIREN. Cardio-respiratory changes and mortality in the conscious rat induced by ( + )- and ( ± )-anatoxin-a. Toxicon 30, 899-905, 1992.-Anatoxin-a (AnTx-a) isapotent nicotinic cholinergic receptor agonist. The relative potencies of the ( + )-AnTx-a and the racemic mixture ( ± )-AnTxa were investigated in the conscious rat by comparing their effects on mean arterial blood pressure (BP), heart rate (HR), blood oxygen and carbon dioxide pressures (p02 and pC02, respective1y), acid-base balance (pH) and mortality. The present experiments show that while both forms of AnTx-a produce dose-dependent increases in BP and decreases in HR, ( + )-AnTx-a is about IO-fo1d morepotent than the optically inactive isomer. ( + )-AnTx-a was also 6-fo1d more potent than ( ± )-AnTx-a in produclog severe hypoxemia, and more than 4-fold as potent as the (±}-AnTx-a in producing significant hypercapnia accompanied with severe acidosis. The approximate median Iethai dose (Ln so) of ( + )-AnTx-a was about 5-fold less than that of ( ± )-AnTx-a. We conclude that ( + )-AnTx-a is more potent than the ( ± )-AnTx-a racemic mixture in causing detrimental cardio-respiratory changes and therefore increased mortality in the rat.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1990,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Cardiovascular effects of anatoxin-a in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63103},
  year      = {1990},
  abstract  = {Cardiovascular Effects of Anatoxin-A in the Conscious Rat. SJREN, A.-L., AND FEUERSTEIN, G. (1990). Toxicol. Appl. Pharmacol. 102,91-100. The effects ofanatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R). and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of anatoxin-A was further compared to nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry. Anatoxin-A and nicotine (30, 100 and 300 1-!g/kg iv) produced an increase in MAP with concomitant bradycardia. The highest doses increased Cl. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the ganglion blocker chlorisondamine (5 mg/kg, iv). Anatoxin-A ( 100 1-!g/k~ iv) increased plasma epinephrine Ievels by 2- fold with virtually no effect on norepinephrine whereas nicotine ( 100 ~oLg/kg, iv) increased plasma epinephrine and norepinephrine by 20- to 30-fold. Central administration of anatoxin-A and nicotine (30-100 ,ug/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that anatoxin-A acts as a nicotinic cholinergic agonist in the c.onscious rat after both systemic and centrat administration. Anatoxin-A and nicotine produced pressor and reno-splanchnic vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation ofthe nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency ofanatoxin-A versus nicotine to stimulate the sympathoadrenomedullary axis.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1988,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63236},
  year      = {1988},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{Siren1988,
  author    = {Sir{\´e}n, Anna-Leena},
  title     = {Cardiovascular pharmacology of thyrotropin releasing hormone},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63214},
  year      = {1988},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{PaakkariNurminenSiren1986,
  author    = {Paakkari, I. and Nurminen, M-L. and Sir{\´e}n, Anna-Leena},
  title     = {Cardioventilatory effects of TRH in anesthetized rats: role of the brainstem},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63277},
  year      = {1986},
  abstract  = {Cardioventilator responses were studied in anaesthetized rats after injections of TRH into either the lateral (i.c.v. lat) or the fourth (i.c.v. IV) cerebral ventricles. TRH induced a morerapid hypertensive effect i.c.v. IV than i.c.v. lat. Blocking of the cerebral aqueduct abolished the hypertensive and tachypnoeic effects of TRH i.c.v. lat but not those of TRH i.c.v. IV. It is concluded that TRH increased blood pressure and ventilation rate via brain stem structures close to the fourtli ventricle.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{VonhofSirenFeuerstein1991,
  author    = {Vonhof, S. and Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63075},
  year      = {1991},
  abstract  = {Thyrotropin-releasing hormonewas shown to exert potent ventilatory effects after centrat 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, CO\(_2\) production CO\(_2\) 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, CO\(_2\) production and O\(_2\) consumption were elevated by 4.6 and 11.7 fold, whiJe no significant changes in locomotor activity were observed. The results suggest that TRH stimulates ventilation by a mechanism independent of its analeptic properties.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{DoronMcCarronHeldmanetal.1992,
  author    = {Doron, D. A. and McCarron, D. M. and Heldman, E. and Sir{\´e}n, Anna-Leena and Spatz, M. and Feuerstein, G. and Pollard, H. B. and Hallenbeck, J. M.},
  title     = {Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63032},
  year      = {1992},
  abstract  = {The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca\(^{2+}\)·ionophore (A23187), or tumor necrosis factor (TNF) and interleukin·l (IL.l). Treatment ofcultured BMECs fron. WKY and SHR with all of these factors dose·dependently increased their total amount of TF; no substantive differences in the Ieveis of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{PaakkariPaakkariVonhofetal.1993,
  author    = {Paakkari, P. and Paakkari, I. and Vonhof, S. and Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Dermorphin analog Tyr-D-Arg\(^2\)-Phe-sarcosine-induces opioid analgesia and respiratory stimulation - the role of Mu\(_1\)- receptors?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62984},
  year      = {1993},
  abstract  = {Tyr-o-Arg\(^2\)-Phe-sarcosine\(^4\) (TAPS), a mu-selective tetrapeptide analog of dermorphin, induced sustained antinociception and stimulated ventilatory minute volume (MV) at the doses of 3 to 100 pmol i.c.v. The doses of 30 and 100 pmol i.c.v. induced catalepsy. The effect of TAPS on MV was in negative correlation with the dose and the maximal response was achieved by the lowest (3 pmol) dose (+63 ± 23\%, P < .05). Morphine, an agonist at both mu\(_1\) and mu\(_2\) sites, at a dose of 150 nmol i.c.v. (equianalgetic to 100 pmol of TAPS decreased the MV by 30\%, due to a decrease in ventilatory tidal volume. The antinociceptive effect of TAPS was antagonized by naloxone and the mu, receptor antagonist, naloxonazine. Naloxonazine also attenuated the catalepsy produced by 1 00 pmol of TAPS i.c. v. and the respiratory Stimulation produced by 3 pmol of TAPS i.c.v. Pretreatment with 30 pmol of TAPS antagonized the respiratory depression induced by the mu opioid agonist dermorphin (changes in MV after dermorphin alone at 1 or 3 nmol were -22 ± 1 0\% and -60 ± 9\% and, after pretreatment with TAPS, +44 ± 11 \% and -18 ± 5\%, respectively). After combined pretreatment with naloxonazine and TAPS, 1 nmol of dermorphin had no significant effect on ventilation. In contrast, pretreatment with a low respiratory stimulant dose (10 pmol i.c.v.) of dermorphin did not modify the effect of 1 nmol of dermorphin. ln conclusion, the antinociceptive, cataleptic and respiratory stimulant effects of TAPS appear to be a related to its agonist action at the mu, opioid receptors. TAPS did not induce respiratory depression (a mu\(_2\) opioid effect) but antagonized the respiratory depressant effect of another mu agonist. Thus, in vivo TAPS appears to act as a mu\(_2\) receptor antagonist.},
  subject      = {Neurobiologie},
  language  = {en}
}