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Biomedical subjects

P Grieb

Publications and source records attributed to P Grieb.

At least 55 records · Page 3Linked to original sources

Determination of 2-bromo and 2-chloro derivatives of 2'-deoxyadenosine in human blood serum by high performance liquid chromatography.

The aim of this study was to determine 2-chloro, and 2-bromo derivatives of 2'-deoxyadenosine (2-CdA and 2-BdA respectively) in the serum of human blood by high performance liquid chromatography (HPLC). 2-CdA is a substance with anticancer and immunosuppressive activity. Caffeine or 5,6-dimethylbenzo-1,2,4-triazole-1-beta-D-ribofuranoside was added to 1 cm3 of serum as internal standard. 2-CdA and 2-BdA were isolated from serum using acetone as deproteinizing reagent. LiChrosorb Si 60 column was used for the separation of drugs and the internal standard from endogenous compounds in the sample. A mixture of potassium dihydrophosphate-methanol was used as a mobile phase.

Chromatography, High Pressure Liquid↗

[Clinical pharmacology of ursodeoxycholic acid (UDCA)].

Ursodeoxycholic acid (UDCA) is frequently confused with chenodeoxycholic acid (CDCA), although its pharmacological properties are quite different, clinical indications much broader and it produces practically no side effects. By several mechanisms (including, inter alia, induction of hypercholeresis and formation of liquid crystals with cholesterol) UDCA decreases bile saturation with cholesterol and increases bile metastability. Upon oral administration UDCA, which is hydrophilic, substitutes for and protects hepatocytes against damage by other more hydrophobic and toxic bile acids. In consequence it exerts hepatoprotective and immunocorrective influence. Clinical efficacy of UDCA in gallstone dissolution and prophylaxis, in treatment of biliary dyspepsias, in chronic active hepatitis, in primary biliary cirrhosis and in other cholestatic liver diseases is reviewed. Other therapeutic indications for the drug are also mentioned.

Animals↗

Successful prevention of neurological deficit in SAH patients with 2-chlorodeoxyadenosine.

Twenty patients suffering from subarachnoid haemorrhage due to ruptured intracranial aneurysm and operated on within 72 h after SAH were treated with an experimental immunosuppressive drug 2-chlorodeoxyadenosine (2-CDA), dose 0.05 mg/kg/day i.v. for 7 days. The 2-CDA treatment was started immediately after angiographic confirmation of ruptured aneurysm, and the standard pharmacological treatment (nimodipine and steroids) was also given. 50% of patients were severely threatened by "delayed vasospasm" or late neurological deficit (Fisher's score 3 or 4). The neurological outcome (assessed 8-12 weeks after SAH) was good (GOS = 1) in 70%, and fair (moderate disability, GOS = 2) in 25%. A single case of severe disability (GOS = 3), as well as two cases of less than perfect outcome (GOS = 2), were related to unusual pre- or intraoperative complications. We conclude that the low doses of 2-CDA can be considered as a valuable adjunct to the standard pharmacotherapy of SAH patients operated on early.

Adult↗

Impaired in vitro proliferative response of suppressor lymphocytes in patients with subarachnoid haemorrhage from ruptured intracranial aneurysm.

Proliferative response to mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen, and other chosen indicators of the activity of the immune system were assayed in peripheral blood mononuclear cells isolated from blood of patients with subarachnoid haemorrhage from ruptured aneurysm. Healthy blood donors served as control group. The SAH group displayed impaired response to concanavalin A, which is a mitogen specific for suppressor cells. It is suggested that the impaired activity of suppressor cells pre-existed in patients with subarachnoid haemorrhage, and after intracranial bleeding it might have contributed to the development of late neurological deficits.

Adult↗

2-Chloro-2' deoxyadenosine prevents angiopathic changes in cerebral arteries in experimental SAH in rabbits.

We compared the morphology of the basilar artery walls in rabbits with experimental subarachnoid haemorrhage (SAH) without and with concomitant treatment with a novel immunosuppressive drug, 2-chloro-2'-deoxyadenosine (2 CdA). The treatment was successful in the prevention of the angiopathic changes, most likely due to its ability to inhibit lymphocyte activation in response to mitogenic signals. Since lymphocyte (and monocyte?) activation may play an important role in the development of the delayed neurological deficits in patients following SAH, the use of 2 CdA to prevent these deficits shall be considered.

Animals↗

Adsorption therapy with tryptophan-conjugated polyvinyl alcohol gels in 10 patients with acute Guillain-Barré syndrome.

In 10 cases of acute Guillain-Barré syndrome selection adsorption (SEA) of immunoglobulins was performed with IM TR350 columns (Asahi Medical, Japan). During this therapy the symptoms of 8 patients were reduced. Side effects were moderate and not specific for SEA. The columns removed large amounts of immunoglobulins, but also eliminated other plasma components.

Acute Disease↗

Plasma exchange and selective adsorption in Guillain-Barré syndrome--a comparison of therapies by clinical course and side effects.

Selective adsorption is a new method of treating Guillain-Barré syndrome. Its therapeutic effects and its concomitant side effects were compared between plasma exchange and symptomatic treatment only. The clinical study of three groups of 10 Guillain-Barré patients, each matched for age and maximal disability, was analyzed. Selective adsorption compared favorably with plasma exchange in shortening the time to first improvement and duration of in-hospital treatment. Side effects were similar in both groups. Symptomatic arteriosclerosis should be considered a relative contraindication for selective adsorption.

Adsorption↗

Evidence for sex steroid receptors in feline brainstem.

Specific binding sites for estrogens, androgens, and progestins were found in cytosol from perfused cat brainstem with the use of a steroid binding assay. These sites resemble 'classical' steroid receptors in ligand specificity as well as in sedimentation properties (sedimentation constant 8-10S on sucrose density gradient). The presence of estrogen receptor in brainstem extracts was also confirmed by an enzyme immunoassay employing monoclonal antibodies directed against human estrogen receptor. This finding may be relevant to known influences of sex steroids on respiration.

Animals↗

HLA antigens and intracranial aneurysms.

The frequencies of the HLA-A, -B and -DR were determined in a group of 59 transplant donors who died from subarachnoid haemorrhage within three days following the rupture of intracranial aneurysm (the SAH group) and compared with those of a control group consisting of 389 donors who died from other causes. The only significant difference was in the increased frequency in the SAH group of non-typed ("empty")-DR loci in association with the DR7 phenotype. The most probable explanation of this finding is that in the SAH group the frequency of DR7 homozygotes is several times higher than in the general population, and that bearing the DR7 allele in homozygotic form is associated with a very high risk of developing potentially fatal intracranial aneurysmal haemorrhage.

Autoimmune Diseases↗

O2 exchange between blood and brain tissues studied with 18O2 indicator-dilution technique.

A technique has been developed to record 18O2 dilution curves of an organ in vivo by use of 51Cr-labeled erythrocytes as a reference tracer. The technique employs anaerobic sampling of venous outflow following an intraarterial injection of tracer-laden blood and off-line determination of [18O2] and [51Cr] profiles in the venous outflow. O2 and reference indicator-dilution curves of cerebral circulation were recorded in eight experiments with six halothane-anesthetized dogs. Autologous blood labeled with the tracers was injected into a carotid artery, and brain venous outflow was sampled from the sagittal sinus. The total net extraction of O2 tracer was equal to the extraction of elemental O2. Instantaneous extraction of 18O2 along the outflow curve fell linearly with time, from an initial value of 0.6-0.7 to very small or even negative values toward the end of a pulse. This indicates that O2 undergoes a flow-limited distribution. In all experiments, the mean transit time of unmetabolized 18O2 was longer than the mean transit time of the Cr tracer. An index of the tissue O2 dilution space, hence the mean tissue PO2, is calculated from this data with the use of a modified central volume principle. This estimate of mean tissue PO2 increases as a linear function of sagittal sinus PO2 with a slope of 0.97. The method may provide an index of the critical PO2 of venous blood, the PO2 below which O2 diffusion from blood to tissue may limit its rate of metabolic uptake.

Animals↗