Biomedical subjects
Publications and source records attributed to W Schulze.
After first describing the course of BCG osteitis in young children, the problems associated with the routine prophylactic BCG inoculation in countries with a low incidence of tuberculosis are discussed. There is good reason to draw attention to the recommendation of the Inoculation Commission attached to the Federal Health Office calling to the fact that newborn infants should be inoculated only if they belong to the high-risk groups.
In W. Germany came the ethology the first time in a law 1972. The way was no easy work.
The aim of the present study was to investigate the influence of different stages of leukemia P388 on the pharmacokinetics of the antineoplastic agent mitoguazone in mice. It could be shown that, independent of the tumor stage investigated, the total clearance of mitoguazone is slightly reduced reflecting a moderate increase of AUC in the serum of leukemia-bearing animals. Furthermore, in an advanced tumor stage the drug levels in kidneys, liver, spleen and serum were found to be elevated to some extent in comparison to tumor-free controls in contrast to an earlier stage of leukemia. In conclusion, the tumor stage has to be considered as an important factor to which extent a neoplasia may alter the pharmacokinetics of drugs used for anticancer chemotherapy.
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The paper gives an overview of the history of the school of vet. med. technicians at the School of Veterinary medicine Hannover.
Normothermic, 3 min lasting perfusion of isolated rat heart with Krebs-Ringer-Henseleit solution in which Ca was replaced by EDTA, followed by successive perfusion of Ca2+ containing medium resulted in structural and metabolic derangement of myocardial cells; this could be demonstrated electronmicroscopically and histochemically. Unlike in ischemia, Ca paradox left the enzymes LDH, SDH, beta-HBDH as well as alpha-glucan phosphorylase and ATP-ases better preserved in the subendocardial layer of the left ventricle. Ultrastructural analysis of this phenomenon showed good correlations with the histochemical findings. A large portion of cardiomyocytes in the subendocardial layer showed only slight changes. On the other hand, myocytes in the subepicardial layer were severely injured and all characteristics of the calcium paradox were present including hypercontraction bands with fusion of myofilaments, extrusion and accumulation of oedematous mitochondria containing electron dense material intracristally, sarcolemmal ruptures, separation of intercalated discs etc. The better preservation of the subendocardial region in experiments with calcium paradox could be explained by inadequate perfusion of this layer with Ca2+ free medium due to transmural anatomical inhomogeneity of the capillary supply, resulting in a better protection of these myocytes from Ca paradox. The heterogeneity in transmural distribution of injuries is a multifactorial phenomenon. In addition to factors such as intramural pressure gradient, transmural pressure, enddiastolic intraventricular pressure etc., the most important factors in both types of injuries should be regarded the amount of vascular supply, blood flow and perfusate volume.
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Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance. M-G seems to be effective especially in combination with other antineoplastic drugs. Its final evaluation may be reserved to further randomized trials. Recently, the psoriasis vulgaris is expected to be an additional field of the application of M-G. In this minireview data on synthesis, preclinical pharmacology, pharmacokinetics, biochemical effects and toxicology of M-G are given. Furthermore, clinical findings on M-G concerning its pharmacokinetic behaviour, antitumor and antipsoriatic activities are described.
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Single and sequential double immunocytochemical techniques were applied to localize gamma-aminobutyric acid (GABA)- and choline acetyltransferase (ChAT)- like immunoreactivity (-LI) in the hypoglossal nucleus of the rat. After subsequential double staining a relatively high number of hypoglossal motor neurons showed the coexistence of both ChAT- and GABA-LI. Coexistence of both substances was also revealed in the axons of the hypoglossal nerve situated within the medulla oblongata. Cells showing only ChAT- or GABA-LI were also observed. Differences in immunostaining between the different cell groups of the hypoglossal nucleus were established. Following axotomy of the right hypoglossal nerve, a decrease or loss of the immunoreactivity for both ChAT and GABA in the motor neurons was established until the 3rd week after the operation. The results obtained do not give evidence on the origin of the GABA-like immunoreactive material and its functional significance in the cholinergic neurons. It can be only speculated that the GABA-like material is either taken up from the intercellular space or is synthesized by the ChAT-LI nerve cells. Functionally, the importance of GABA for the synthesis of gamma-hydroxybutyrate (a novel neurotransmitter candidate) and its postsynaptic transmitter action or presynaptic regulatory action (through autoreceptors in the membrane of the nerve endings) on the release of acetylcholine (ACh) should be taken into consideration.
Correlations between the manifestation of obstructive sleep apnoea syndrome (OSAS) and anatomical or functional changes in the upper respiratory tract remain controversial. The correlation between obstruction of the upper respiratory tract and the degree of sleep apnoea syndrome was investigated in 60 patients with obstructive sleep apnoea (diagnosed by polysomnography) and in 55 healthy controls. After clinical examination, rhinomanometry and determination of the size of the lower jaw and oropharynx, the motility of the pharyngeal walls during Mueller's manoeuvre was evaluated by flexible endoscopy. No significant anatomical or functional differences were observed between OSAS patients and healthy controls. There was no correlation between the degree of OSAS (expressed by the apnoea index) and pharyngeal size. Although no specific statement concerning diagnosis or degree of OSAS can be made on the basis of an otolaryngological examination, OSAS patients should always undergo otolaryngological examination to exclude pharyngeal disease.
Important properties of p-(thiosemicarbazido)diamino-methylen-hydrazino benzene (1; dihydroambazone) are described. The transformation of this compound into 1,4-benzoquinone guanylhydrazone thiosemicarbazone (2; ambazone) dependent on different aqueous buffer systems was investigated. The spectroscopic behaviour of the transformation product allows us to determine the content of the compound in aqueous solutions, whereas the determination in serum is much more difficult. Furthermore, TLC experiments and oxidation methods are described.
In rats, the pharmacokinetics of 14C-ambazone after i.v. and oral administration was studied. The results demonstrate that the compound is incompletely absorbed from the gastrointestinal tract, penetrates rapidly and to a high degree into various tissues and is preferentially eliminated via the kidneys. After i.v. administration of 50 mg/kg b.m. disposition half-life in whole blood is about 6-7 h. The extent of absorption from the gastrointestinal tract is about 40%.
There is some evidence in the literature that the pharmacokinetics of anticancer agents can be influenced by the presence of a tumor. Therefore several authors recommend pharmacokinetic studies of such drugs to be performed also in tumor-bearing animals (2, 5, 7). The aim of the present study was to evaluate the influence of different stages and routes of inoculation of leukemia P 388 in B6D2F1-hybrid mice on the tissue distribution of ambazone, a new potential antineoplastic drug. It could be emphasized that the drug levels in liver, kidneys and thymus were higher in advanced tumor-bearing than in control animals whereas in the spleen and in whole blood the opposite was true. The differences can be explained partially by changes in the erythrocyte binding of ambazone.
Using the immunocytochemical peroxidase-antiperoxidase method we observed strong and selective staining of Leydig cells after incubation of human testicular tissue with an antiserum against substance P and a slightly weaker immunoreactivity against methionine-enkephalin. These results indicate that the embryologic origin of Leydig cells may require reconsideration and also offer a new perspective for research upon the local control mechanisms of spermatogenesis.
Calcium transport mediated by the sarcolemma (SL) Na+-Ca2+ exchanger and by the sarcoplasmic reticulum (SR) Ca2+ pump were studied in crude membranes from ventricular tissue of newborn and young rat, adult frog, guinea pig, chick, hamster, Rhesus monkey, rabbit, and pig. Transport activities were evaluated per mass of membrane protein and heart tissue. Relative to unit of ventricular mass Na+-Ca2+ exchange activity (at [Ca2+] = 75 microM) is highest in newborn rat, frog, guinea pig, and chick amounting to about 17.7, 17.5, 16.2, and 10.1 mumol Ca2+/kg wet weight/2s, respectively. Considerable lower values were obtained in the other species. The lowest Na+-Ca2+ exchange rate was found in 40-day old rat amounting to 2.4 mumol Ca2+/kg wet weight/2s. Parallel determination of active SR Ca2+ uptake in the same membrane preparations reveals that the quantitative relationship between the two different Ca transport processes is not invariant with respect to species and stage of differentiation. The data suggest that Ca2+ handling in small-sized cardiac cells with poorly developed SR (newborn rat, frog) depends to a greater extent on Ca2+ fluxes via the SL Na+-Ca2+ exchanger as compared to differentiated cardiac cells of adult mammalian and avian species. By contrast, the contribution of SR Ca2+ transport to cardiac Ca2+ movements becomes more predominant in differentiated cardiac cells.