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Biomedical subjects

S Bittner

Publications and source records attributed to S Bittner.

31 records · Page 2Linked to original sources
PubMed1989

[The critical 3-day fever-exanthema in young children (exanthema subitum, Zahorsky roseola infantum)--what is new?].

As to the present knowledge the critical rose rash of infants (exanthema subitum, roseola infantum) means to be an exanthematous infectious disease that, occurring preferably in elder babes and younger infants (1st--3rd year of life), is caused by the newly detected herpesvirus (now the sixth one) pathogenic for man. The natural contamination in our latitude is intense (60-75%), and the probably lifelong immunity in the majority of cases is acquired in infancy. Though experts in the clinical subject do stress all the time the exanthema subitum to be the most frequent exanthematous disease in early infancy and infancy, infection chains tested to exanthema, respectively epidemics are observed decidedly seldom. Consequently, most of all infections use to develop clinically inperceptibly or even with other symptoms (and without an exanthema); the exanthema up to now obligatory for establishing the diagnosis uses to appear only in the minority of all cases and in the great majority of them the seroconversion is clinically silent. The prognosis of the exanthema subitum is in force to be good; the disease is the special field of activity for ambulatorily acting physicians (paediatrist, general practitioner). To begin with, the status diagnostically unclear and high-febrile for several days, the central-nervous excitability occurring in many cases, and in some children the appearing of dramatic febrile convulsions, as well as gastroenteric symptoms perpetually give rise to differential diagnostic considerations and sometimes even to a (false) antibiotic therapy. In case of an affection by herpesviruses principally a latency (persistence) of the virus lasting for years (possibly even lasting for life) in human beings is to be taken into account; this condition is also current for HHV 6. On occurring of an immune debility a release and a discharge of herpesviruses--not only by children suffering from an exanthema subitum (!)--are possible so that human beings of each age may come into question to be the source of infection. Double infections of human immune cells (for instance HHV 6 and HIV 1 simultaneously) already have been found. The necessary studies in order to clarify essential clinical and virological problems are world-widely in full activity, and new cognitions (further symptoms of diseases associated with HHV 6, possibly affections in prenatal infections and so on) are soon to be taken into account.

Child, Preschool↗
PubMed1988

Glucocorticoid-induced lymphoma cell growth inhibition: the role of leukotriene B4.

Glucocorticoid-sensitive murine S49.1 lymphoma cells respond in a biphasic way to the steroid challenge. The first effect of corticosteroids is to induce a reversible growth inhibition, which is probably permissive for the following cytolysis. Distinct mechanisms for the two effects are likely. Since dilution of S49.1 lymphoma cultures resulted in a drastic reduction of the proliferation rate, which could be overcome by the addition of conditioned medium, the proliferation appears to depend on the presence of autocrine growth factors. Therefore, the cytostatic effect of corticosteroids could possibly be attributable to an interference with the production of endogenous growth factors. Analysis of the growth-promoting activity in culture supernatant showed that the critical growth factor in diluted cultures is an arachidonic acid metabolite, the leukotriene B4. The role of leukotriene B4 in S49.1 cell proliferation received further support from the finding that while nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway which is necessary for leukotriene formation blocked lymphoma multiplication, indomethacin, an inhibitor of cyclooxygenase activity, did not affect proliferation. Quantitation of the leukotriene B4 content of dexamethasone-treated vs. untreated cultures revealed an almost complete inhibition of leukotriene production, pointing to the significance of this mechanism for the glucocorticoid-induced lymphoma growth inhibition. Moreover, these findings offer a new approach to increase the therapeutic effectiveness of glucocorticoid therapy of steroid-sensitive leukemias and lymphomas.

Animals↗
PubMed1985

New class of inhibitors specific for human renin.

Seven active tetrapeptide amides characterized by a C-terminal phenylalanyl aminoadamantane (PheNHAd) sequence, were identified by selective testing for human renin inhibitory activity among compounds with adjacent hydrophobic groups and molecular size equivalent to 3-5 amino acid residues. The new inhibitors were compared with known renin inhibitors (RIP, pepstatin, H-77) and opioid analgesic agents (Met-enkephalin, morphine), with the following results: The new inhibitors were active against human renin (IC50 approximately 10-5M), but inactive against rat renin and pepsin. Although active in opiate receptor binding studies (IC50 approximately 10(-7)M), they were, with few exceptions, inactive in the mouse writhing and hot plate tests for analgesia. SAR studies suggested a separation of the renin inhibitory from the analgesic activity of enkephalin analogs. Preliminary experiments with sodium-depleted rhesus monkeys indicated hypotensive activity for three of the new inhibitors at 3 mg/kg i.v., and RIP at 1 mg/kg. The recently reported clinical hypotensive properties of RIP (Zusman et al., Trans. Assoc. Am. Physicians 96:365, 1983) along with the present comparative studies suggest that the new inhibitors may lead to clinically useful agents.

Amantadine↗
PubMed1980

Differences in enzyme efflux from dystrophic mouse skeletal muscle and heart.

The efflux of the enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) from isolated normal and dystrophic mouse (C57BL/6J-dy) skeletal muscle and heart has been studied. Older (5-9 months) dystrophic mouse triceps contained only 63% of normal CK. At 3.5-10 weeks, dystrophic gastrocnemii had 72% and 61% of normal for males and females, respectively. By 5-7 months, the levels dropped to only 26% and 15% of normal. When skeletal muscle efflux was normalized to enzyme content, dystrophic muscle was not significantly different from normal for the first three hours, and was lower than normal in the 3-5 hour period. This was true for both triceps and gastrocnemius. Similarly, no difference in LDH efflux from gastrocnemius was seen between control and dystrophic mice. In contrast, there was no difference in enzyme concentration of normal and dystrophic hearts. Despite this, hearts from dystrophic mice had a higher efflux of both CK and LDH in the first three hours, but not beyond. The results indicate that under the conditions of these studies, dystrophic skeletal muscle was not, but heart was, more permeable to muscle enzymes than normal muscle.

Animals↗
PubMed1979

Factors influencing mouse heart creatine kinase efflux and ultrastructure.

An isolated mouse heart model has been developed to study the extracellular factors which influence the loss of myocardial enzymes. When added to a tris-HCl buffer/salt mixture at 25 degrees C, glucose, phosphate ion, increased osmolarity, oxygen exclusion and calcium reduced enzyme leakage. Of these, calcium effects on enzyme leakage and ultrastructure were assessed in detail. Concentrations less than or equal to 10(-4) M had no significant effect on enzyme efflux over a 5 hour period. At higher concentrations (10(-3) and 10(-2) M Ca2+), creatine kinase (CK) efflux was significantly altered in a time dependent fashion. In the first hour, 10(-3) and 10(-2) M Ca2+ reduced CK leakage to 33% and 25% of the control values, respectively; and to about 50% of the control values in the second and third hours. This protective effect was lost between the third and fifth hours, when an enzyme efflux 80% greater than control was observed. These studies indicated that CK leakage from mouse heart can be retarded for up to 3 hours by appropriate Ca2+ concentrations. The initial ultrastructural change, in the absence of Ca2+, was a dilatation of the transverse tubules, which gradually enlarged by coalescence. This was followed by a gradual disintegration and ultimate condensation of the myofibrils leaving altered mitochondria floating freely in an apparently intact sarcolemmal bag. These changes appeared to be delayed by Ca2+ for 3 hours, after which no protective effect was evident. Thus, CK leakage is a measure of myocardial autolysis, and numerous simple measures can retard this autolysis for several hours. This raises the possibility of prolonging the preservation of the normal heart in vitro.

Animals↗
PubMed1977

[Inhibition of uterine contraction in emergencies (author's transl)].

During the first stage of labour 48 parturients were treated with the tocolytic agent TH 1165 a (Fenoterol-hydrobromide) because of danger to the foetus. The product was slowly injected i.v. in doses of 50 mcg (35 pat.) and 25 mcg (9 pat.) and on 4 patients in doses of 35 mcg. We investigated the effects of this therapy on labour, on the mother's and the child's circulation and on the foetal acid-base balance and foetal gas partial pressure. Whilst the different TH 1165a doses were not markedly different in their tocolytic effect, we discovered that side-effects occurred considerably more often and more intensively when higher doses of TH 116A WERE ADMINISTERED. We therefore recommend one i.v. injection of 25 mcg TH 1165a for clinical uterine relaxation in emergencies during labour. To guard against a vena cava compression syndrome, the injection should always be given with the patient in a lateral position. In emergency uterine relaxation the cardiac tocography (supplemented if necessary by micro blood gas analysis) should be monitored. In order tnce-only syringe containing 25 mcg TH1165a.

Blood Gas Analysis↗
PubMed1977

Penicillamine effects on enzyme efflux from skeletal and heart muscle.

We have previously shown that pretreatment of mice with diethylstilbestrol (DES) or prednisolone (Pr) lowered enzyme efflux from isolated mouse skeletal muscle. These same agents also lowered the high serum enzyme activities in boys with Duchenne's muscular dystrophy (DMD). In a continuing search for other agents with similar effects, the influence of penicillamine (Pe) on enzyme efflux from isolated muscle was assessed, because it lowered the high plasma creatine phosphokinase (CPK) and produce beneficial effects in avian muscular dystrophy. Three groups of mice received 0, 1, or 10 mg Pe daily for 14 days. All mice were given supplementary pyridoxine. The egress of CPK and lactate dehydrogenase from the isolated left gastrocnemius and heart was determined over a 5 hour period. Pe produced more modest effects than did DES or Pr. The 10 mg dose reduced enzyme efflux from the gastrocnemius by 10%. In contrast, heart enzyme efflux was augmented by 20%. Similar dose-related disparate effects on enzyme efflux from skeletal muscle and heart have been previously noted for DES and Pr. Pe is the third agent found to lower the high serum enzyme activities in muscular dystrophy and reduce gastrocnemius enzyme efflux from isolated mouse skeletal muscle. This further establishes the usefulness of the mouse assay for identifying agents that lower the high serum enzyme activities in muscular dystrophy.

Animals↗
PubMed1977

Abolition of the diethylstilbestrol reduction of enzyme leakage from muscle by a 3,3' diallyl substitution.

Diethylstilbestrol (DES) lowers enzyme efflux from isolated mouse skeletal muscle. It also lowers the high serum enzyme activities in Duchenne's muscular dystrophy. We have begun a systematic study of DES congeners, to identify those portions of the DES molecule which are critical to these effects, and to tailor a molecule which might have fewer feminizing effects. The first compound tested was the 3,3' diallyl derivative of DES (DAS). It was selected because previous reports indicated that it was as anabolic as DES, but only 1/10 to 1/30 as estrogenic. Doses of 20, 100 and 250 microgram/mouse/day were administered in 0.05 ml sesame seed oil vehicle to C57BL/6 mice. Control animals received only the vehicle. In contrast to DES which has consistently reduced muscle enzyme efflux 30-50%, DAS was inert. The substitution of the two allyl groups in the 3 and 3' positions blocks access to the neighboring ethyl groups and partially covers the two phenolic hydroxyl groups of DES. This suggests that these molecular sites have pertinence to the reduction of enzyme efflux from mouse skeletal muscle by DES, and possibly the reduction of the high serum enzyme activities in Duchenne's muscular dystrophy.

Allyl Compounds↗
PubMed1976

Disparate effects of diethylstillbestrol and prednisolone on enzyme efflux from heart and skeletal muscle.

We have previously shown that diethylstilbestrol (DES) almost always, and prednisolone (Pr) less frequently, lowered the high serum enzyme activities in Duchenne's muscular dystrophy (DMD). In experimental studies, it was shown that pretreatment of mice with each of these agents lowered enzyme efflux from isolated skeletal muscle incubated in vitro, but efflux was augmented by higher doses of Pr. This suggested that these agents may influence skeletal muscle enzyme efflux in man also, producing the effects noted in DMD. The present studies were undertaken to assess the effect on enzyme efflux from skeletal muscle and heart that these two agents would exert when given in combination. Four groups of mice (14/group) were injected with saline, 250 mug DES, 35 mug Pr, or 250 mug DES plus 35 mug Pr in saline every other day for 22 days. The left gastroecnemius and heart were isolated from animals of each group, and placed in separate tubes containing incubation medium at 25 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which issued from each organ was determined over a 5 hour period. In the doses tested, it was found that: 1) DES selectively reduced enzyme efflux from skeletal muscle, but had no effect on enzyme efflux from heart; 2) a Pr dose which decreased enzyme efflux from the heart, augmented efflux from the gastrocnemius; and 3) DES prevented the enhanced enzyme efflux produced by Pr. These studies indicate that these hormones, in pharmacological doses, influence enzyme efflux from muscle. This suggests, but it is not established, that these hormones also exert a similar physiological role. Finally, this experimental model appears to be useful in assessing the effects of single agents, and agents in combination, on enzyme efflux, and should be of aid in selecting appropriate agents which may be therapeutically useful in Duchenne's muscular dystrophy.

Animals↗
PubMed1973

Increase in Free and Bound Abscisic Acid during Natural and Ethylene-induced Senescence of Citrus Fruit Peel.

Free and bound abscisic acid and neutral growth inhibitors were detected in citrus fruit peel using two bioassays and gasliquid chromatography. None of the inhibitor components seems to be directly associated with chloroplasts or chromoplasts in citrus fruit peel.Green, nonsenescent fruits contain mostly neutral inhibitors and relatively low amounts of free and bound abscisic acid. Upon harvest and storage in ethylene, 50 microliters per liter, both free and bound abscisic acid accumulate rapidly, attaining within 24 hours a level of 1 microgram per gram. After 48 hours bound abscisic acid reaches a much higher level than free abscisic acid. Fruits allowed to senesce on the tree follow a similar course of abscisic acid accumulation, attaining finally a 10: 1 ratio of bound to free abscisic acid.

Journal Article↗
PubMed1971

Abscisic Acid and cytokinin contents of leaves in relation to salinity and relative humidity.

The question is raised whether the hormonal modifications in a plant exposed to osmotic root stress result directly from the decrease in water potential of the root environment or from disturbances of the plant's water balance.Tobacco plants were held for 24 hours under either high or low relative humidities, with or without salt. The amount of abscisic acid in the leaves of salinized plants rose markedly in low, but not in high, relative humidity. No change in the amount of extractable cytokinins was detected in any treatment. It is tentatively suggested that variations in the water content of leaves constitute a primary signal for modification of plant hormonal balance.

Journal Article↗