Biomedical subjects

S Bittner

Publications and source records attributed to S Bittner.

5 recordsLinked to original sources

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↗