Search PubMedSearch

Biomedical subjects

T Schubert

Publications and source records attributed to T Schubert.

12 recordsLinked to original sources

Levoprotiline ((-)-oxaprotiline) effects on inositol phosphate generation in human peripheral lymphocytes.

The effects of the atypical antidepressant levoprotiline (LPT) on inositol phosphate metabolism were investigated in N-formyl-methionyl-leucylphenylalanine (fMLP) activated human lymphocytes. In the presence of LPT, stimulation of phosphoinositide hydrolysis by fMLP lead to an increased accumulation of inositol bisphosphates, an effect which could be detected within the range of therapuetic plasma concentrations and which is exerted by lithium in a similar way. Furthermore, incubation of lymphocytes with LPT and subsequent stimulation with fMLP lead to a pronounced decrease in the level of free intracellular [3H]inositol. Both LPT effects, the increased accumulation of inositol bisphosphates and the reduction of free intracellular [3H]inositol, were found to be more pronounced for LPT than for its enantiomer (+)-oxaprotiline. The results are discussed in view of a possible biochemical mechanism which may contribute to the antidepressive activity of LPT.

Antidepressive Agents

Therapeutic concentrations of lithium and carbamazepine inhibit cGMP accumulation in human lymphocytes. A clinical model for a possible common mechanism of action?

Although a large variety of biochemical effects have been reported for lithium (Li) and carbamazepine (Cbm), the final molecular mechanism underlying their therapeutic efficacy for recurrent affective disorders is still unknown. The data presented here clearly indicate that therapeutic concentrations of both drugs inhibit sodium nitroprusside-induced accumulation of cGMP in human lymphocytes to about the same extent. The effect is not seen for other antidepressants, and shows pronounced interindividual variations in healthy volunteers. A similar effect of lithium and carbamazepine can also be demonstrated for the cGMP accumulation of central neurons using the model of dissociated cells of the mouse brain. The results are discussed in view of a common mechanism of action of both drugs. Furthermore, it is speculated that the individual sensitivity of the cGMP generating system of human lymphocytes to both drugs might be used to predict therapeutic response or nonresponse of the individual patient.

Animals

[Modification of tear film break-up time by beta blocker eyedrops without preservatives].

Traditional beta-blocking eye drops preserved with benzalkonium chloride show an adverse effect on the precorneal tear film, which can be measured by checking the break-up-time (BUT). To decide, whether this adverse effect is caused more by the beta-blocking drug or the preservative, we tested the influence of timolol eye drops without preservative in single dose units Timosine) on the BUT in a prospective, open study. These eyedrops caused no significant shortening of the BUT in persons, which where untreated before. Patients using preserved beta-blocking eye drops and having irritations of their eyes showed significant prolongation of the BUT after changing the therapy to Timosine. Preservative-free beta-blocking eye drops are a real improvement in the therapy of glaucoma patients with irritated eyes.

Glaucoma

Central cholinergic functioning and aging.

Normal aging in experimental animals and humans has been demonstrated to affect various aspects of central cholinergic functions. Although deficits at the levels of the number of cholinergic neurons, the acetylcholine synthesis, and the number of muscarinic cholinergic receptors are probably less relevant, deficits at the levels of acetylcholine release, muscarinic cholinergic receptor plasticity, as well as muscarinic cholinergic receptor function are fairly pronounced and seem to justify the assumption that the functioning of the central cholinergic system is impaired by aging. However, whether these cholinergic deficits of normal aging are the sole neurochemical basis to explain age-associated memory impairment or whether other transmitter systems also play a role is still a matter of controversy.

Aging

Lithium but not cholinergic ligands influence guanylate cyclase activity in intact human lymphocytes.

The presence of guanylate cyclase in intact circulating human lymphocytes and the sensitivity of this enzyme to stimulation by sodium nitroprusside could be confirmed. However, in contrast to other observations all attempts failed to stimulate the enzyme by cholinergic agonists, despite the use of M1 as well as M2 selective agonists. These findings do not support the assumption that cholinergic recognition sites on human lymphocytes described by many groups are part of a functioning muscarinic transducing mechanism. While several other neuroreceptor agonists were also unable to affect lymphocyte guanylate cyclase activity, lithium was found to potently inhibit the stimulation of guanylate cyclase by sodium nitroprusside at an intracellular concentration close to the therapeutic plasma levels. It is suggested that the effects of lithium on guanylate cyclase activity in human lymphocytes could be related to a possible mechanism of action of lithium in affective disorders.

Adult

[Plate osteosynthesis of the femur in patients with multiple and mono-trauma].

In multiple trauma patients successful treatment of femur shaft fractures depends more on timing of osteosynthesis than on choosing a specific type of fracture stabilization. Because of theoretical and practical reasons early osteosynthesis within 24 to 48 hours seems to be advantageous. In our experience it led to a significant decrease in complications. However, concomitant thorax trauma mandates special consideration. The two fatalities in our study belonged to this subgroup. With adequate indication for therapeutic intervention, correct operative technique and consideration of the patient's general status good results can be expected with every type of fracture treatment available (external fixation, plate fixation, intramedullary nailing).

Adult

[Use of UV radiation for the disinfection of water. V. Microbiological studies of the behavior of bacterial cells from the logarithmic and from the stationary phase in cold and warm drinking water].

The u.v.-susceptibility of E. cloacae, E. coli and E. faecium was tested with a flow-through u.v. light treatment apparatus. Drinking water of three ranges of temperature (ca. 13 degrees C, ca. 33 degrees C, and ca. 48 degrees C) was used. The u.v.-susceptibility was tested with bacteria harvested in the exponential phase of growth as well as with bacteria harvested in the stationary phase. In all ranges of temperature and both phases of growth reductions of at least 99.9999% of E. cloacae and E. coli were obtained by a dosage of less than or equal to 25 mWs/cm2. For E. faecium harvested in the exponential phase of growth this could be confirmed in cold water of 13 degrees C, while in warm water of 48 degrees C a dosage of ca. 47 mWs/cm2 for a reduction of 99.9999% was necessary. To kill E. faecium-cells, which were harvested in the stationary phase, dosage between 39 and 45 mWs/cm2 were necessary in water of the three ranges of temperature.

Bacteria

[Hypothermia and polytrauma. A case report (28 degrees C)].

In a 29-year-old polytraumatised motorbike driver, massive blood transfusion led to a decrease of the body temperature to 28.1 degrees C rectal on the second day after admission. We could rewarm the patient using only a Clinitron bed, although he had persisting blood loss due to an intravasal coagulopathy. This method has proven to be noninvasive, effective and without any side effects.

Adult

Endoscopic therapy and early elective operation as a therapeutic regimen in ulcer bleeding.

In a prospective protocol we treated 63 consecutive patients admitted to our surgical department with bleeding gastroduodenal ulcers between January 1986 and December 1987. The therapeutic regimen included emergency endoscopy in all cases. Active Forrest Ia or II hemorrhage was treated endoscopically with submucosal injection. Endoscopic control of hemorrhage was achieved in all but one case. Low-risk ulcers, e.g. Forrest II without visible vessel and III or ulcers caused by antirheumatic drug medication were treated definitively by therapeutic endoscopy (31 patients). Ulcers with high risk of rebleeding even after endoscopic therapy underwent additional early elective operation. Thirty patients were treated surgically by this means. Two patients required emergency operation because of failure to control the bleeding (Ia and second rebleeding) endoscopically. The overall mortality of the surgically treated patients was 6% (2/32). The mortality of the therapeutic endoscopy was 0%. Thus, the mortality of the overall group was 3%. The major advantages of this concept were: low mortality rates, elimination of rebleeding in the follow-up period, optimal conditions for the surgical therapy resulting in low death-rates and a reduced need for transfusions.

Adult

[Colonization of the mouse liver by transplanted virogenic leukemia cells. Electron microscopic investigations (author's transl)].

Cells of a virogenic, immature myelogenic leukemia were injected in i.p. in one week old mice, strain NMRI, each animal receiving 10(5), 10(6) or 13(7) cells respectively in 0.2 ml Hanks' BSS. Mice were sacrificed at different times between 10 hrs and 21 days p.i. and liver specimens were prepared for electronmicroscopic studies. 10 hrs p.i. the leukemic cells are found in the sinusoids of the liver and after 30 hrs in the periportal fields. The leukemia cells migrate into the Disse spaces from the sinusoids. The leukemic cells penetrate with cytoplasmic digitations between connected endothelial cells. There is no lytic disintegration of the endothelial cells. The leukemic cells multiply by mitotic division of the Disse spaces, thereby compressing the liver cells. The cell membranes of both cell-types remain intact. Electronmicroscopically no evidence is found of a secretion of enzymes from the leukemia cells that destroy liver cells. Destruction of the liver cells is the consequence of the growth-pressure exerted by the dividing leukemic cells. Within the liver of the recipients the leukemic cells produce RNA-viruses. In the cytoplasm - frequently in the area of the Golgi-field - groups of immature A-particles are formed. In the virus fields the ribosomes disappear. The immature A-particles consist of two concentric electron dense shells. On the surface of the liver cells budding particles and immature C-particles develop. Extracellular mature C-particles with a homogeneous nucleoid and an irregular outer shell may be seen. The formation of viruses is found to be independent of the stage of the leukemia.

Animals

Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment.

The effect of aging on muscarinic cholinergic receptor function in dissociated cell aggregates of the mouse brain was investigated using two biochemical models, i.e., carbachol-induced accumulation of inositol monophosphates and carbachol-induced desensitization of muscarinic cholinergic receptors as measured by the sequestration of specific 3H-N-methyl-scopolamine binding. While aging strongly reduced carbachol-induced inositol monophosphate accumulation, desensitization was not affected in the brains of aged animals. Chronic treatment of aged mice with the nootropic drug piracetam (500 mg/kg daily PO) significantly elevated the agonist-induced accumulation of inositol monophosphates possibly by increasing the available number of muscarinic cholinergic receptors not being in a desensitized state. The results support the hypothesis that nootropics like piracetam might act in part by restoring age-related deficits of central muscarinic cholinergic receptor function.

Aging