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Biomedical subjects

P Grieb

Publications and source records attributed to P Grieb.

66 records · Page 4Linked to original sources
PubMed1979

Relationship between arterial and cisternal CSF oxygen tension in rabbits.

Oxygen tension was measured in samples of blood and cisternal cerebrospinal fluid taken from anesthetized, paralyzed, and mechanically ventilated rabbits at various levels of arterial PO2. Cerebrospinal fluid oxygen tension (CSF PO2) was correlated with arterial PO2 (linear regression equation PCSFO2 = 0.2472 Pao2 + 42.34). During hypoxia CSF PO2 was higher than arterial PO2 in most experiments. These data can be attributed to the Bohr effect, which would increase the PO2 of the blood in choroid plexus capillaries as a result of its acidification. The acidification was suggested by Maren (Am. J. Physiol. 222: 885-889, 1972) to be a part of the ionic exchanges involved in cerebrospinal fluid formation. Such a mechanism may be of importance for supporting choroid plexus metabolism and function during hypoxia. This mechanism is most clearly seen in the rabbit.

Acid-Base Equilibrium↗
PubMedDate not supplied

Cladribine (2-chloro-deoxyadenosine, CDA): an inhibitor of human B and T cell activation in vitro.

We have previously shown that the novel immunosuppressive agent cladribine (CDA) inhibits human T and B cell lymphoproliferative responses and immunoglobulin synthesis in vitro, yet appears to be particularly efficacious as an inhibitor of B cell responses. We now report the effects of CDA on the human mixed lymphocyte reaction and on expression of T and B cell activation markers. CDA produced a significant inhibition of lymphocyte proliferation in human mixed lymphocyte reactions at a concentration of 10 nM. At concentrations of 10-100 nM the drug inhibited phytohaemagglutinin-induced expression of CD25 and HLA-D (by approximately 50%), but not phorbol myristate acetate-induced expression of CD69 on purified human T cells. At a concentration of 10 nM CDA totally abolished Staphylococcus aureus Cowan-induced expression of CD25 on purified B cells. These findings confirm that CDA is a potent immunosuppressive agent with some selectivity towards B cells. The drug may have potentially wide applications in clinical immunosuppression.

B-Lymphocytes↗
PubMedDate not supplied

Changes in oxidative stress in the rat brain during post-cardiac arrest reperfusion, and the effect of treatment with the free radical scavenger idebenone.

The study was designed to determine the effect of idebenone, an electron-trapping agent and free radical scavenger capable of crossing the blood-brain barrier, on cardiac arrest-induced oxidative brain stress. Stress indices used were the brain contents of thiobarbituric acid-reactive material (TBAR), conjugated dienes and protein and non-protein thiols. Twenty-four hours after receiving one oral dose of placebo or 100 mg kg(-1) idebenone, the rats were anaesthetized with diethyl ether and either decapitated immediately, or subjected to 7.5 min cardiac arrest induced by compression of the heart vessel bundle. The next groups of rats were sacrificed at the end of the cardiac arrest session, or resuscitated by external chest compression and artificial ventilation with air and sacrificed 15 min, 60 min, 24 h, and 72 h later while re-anesthetized with diethyl ether. Subsequent placebo or idebenone (100 mg kg(-1)) doses were given to the appropriate surviving rats once daily, beginning 8-10 min after the end of cardiac arrest session. Compared to pre-arrest values, TBAR and conjugated dienes' contents increased, respectively, by 339 and 286%, and protein and non-protein thiol contents decreased, respectively, by 69 and 85% within 60 min after the resuscitation in placebo-treated rats. Normalization of all oxidative stress indices in these rats was slow and incomplete even at 72 h. Idebenone treated rats showed no increase in TBAR contents, and a marked attenuation of changes in the other indices. These results show that oral idebenone greatly reduces oxidative brain stress following transient circulatory arrest in the rat. This effect could not be explained by simple stoichiometric scavenging of free radicals. Possible mechanisms of idebenone action are discussed.

Administration, Oral↗
PubMedDate not supplied

Brain tolerance and preconditioning.

In this review article the authors describe a phenomenon of "brain tolerance" which represents transient resistance of brain tissue to a lethal insult established by preconditioning with a mild insult of short duration. Tolerance evoked by brief ischemia resembles transient ischemic attack(s) (TIA) often preceding full-blown ischemic stroke in a clinical setting. A series of recent studies have described another relevant phenomenon termed "chemical preconditioning". Several substances interfering with cellular energy metabolism applied in subtoxic doses may provide protection against lethal insults of a different type. For example, 3-nitropropionic acid (3-NP), antibiotics erythromycin and kanamycin, acetylsalicylic acid, and 2-deoxyglucose have been shown to evoke tolerance. Recently, we have reported that NMDA receptor antagonists and 2-deoxyglucose used at relatively low doses were potent agents to potentiate the protective anticonvulsant effect induced by transient brain mild ischemia. Further studies are expected to prove similar action of these drugs in other experimental models. Based on the accumulated experimental and clinical data the brain tolerance subsequently reinforced by pharmacological intervention might become a successful prophylactic strategy against serious brain insults in patients.

Brain↗
PubMedDate not supplied

Antioxidant systems--physiology and pharmacotherapy trends.

Metabolic processes connected with the effects of oxidation and antioxidation with participation of cellular energy are presented and therapeutic possibilities connected with coenzyme Q and N-acetylcysteine are discussed.

Antioxidants↗
PubMedDate not supplied

[Treatment of multiple sclerosis with cladribine (2-CDA), a new immunosuppressant agent. Theoretical basis and preliminary results].

The rationale for immunosuppressive treatment of multiple sclerosis comes from current concepts of pathogenesis of this disease. However, clinical effects of immunosuppression have been largely disappointing. Cladribine (chloro-2'-deoxyadenosine, 2CdA) is a new antileukaemic drug which also shows a strong immunosuppressive activity in vitro and in vivo. Being successfully used to treat lymphoproliferative diseases during last few years, cladribine is currently tested in multiple sclerosis. Preliminary results of two independent randomized, placebo-controlled trials are very promising. The indicate that treatment with cladribine may halt the progression of chronic progressive MS, and decrease the frequency of relapses and improve neurological status in remitting-relapsing stage of the disease.

Blood-Brain Barrier↗