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Biomedical subjects

K Masek

Publications and source records attributed to K Masek.

At least 91 records · Page 5Linked to original sources
PubMed1983

Opposite effects of the synthetic immunomodulator, muramyl dipeptide, on rejection of mouse skin allografts.

The influence of muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine) on the rejection of mouse skin allografts was investigated. While the 0.1-mg dose administered on days 7, 6, 5 prior to transplantation caused significant prolongation of the graft survival, the 0.5-mg dose administered on days 3, 2, 1 prior to transplantation resulted in remarkable augmentation of the graft rejection. The present results support the view that muramyl dipeptide can induce both stimulatory and suppressive immune mechanisms, depending on the treatment regimen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Biotransformation of drugs in rats treated with a synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP).

Natural immunoadjuvant mixtures like BCG and FCA are known to produce gross alterations of drug-metabolizing systems in the rat. Since it has been shown that the smallest structure of various bacterial peptidoglycans, possessing adjuvant activity, is muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), the possibility has been tested whether this substance is involved in production of the observed metabolic changes. Synthetic compound was applied subcutaneously for the period of 21 days, and the in vitro activity of 7-ethoxycoumarin-O-de-ethylase, aminopyrine-N-demethylase, together with the microsomal content of cytochrome P-450 and b5, and the in vivo acetylation of sulphadimidine, were investigated. No effect of MDP on any of these tests was noted in both the Lewis arthritic strain and the AVN disease-free strain. It is suggested that MDP is metabolically inactive and that the defects in metabolism of drugs, following bacterial-adjuvant treatment, are likely to be due to some additional cell-wall components, other than peptidoglycans. Furthermore, our data support the view of no relationship between the development of metabolic changes and the established arthritic lesions in rats.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Posttetanic potentiation at the neuromuscular junction of the guinea-pig ileum longitudinal muscle strip: influence of calcium, temperature, ouabain and hexamethonium.

The effect of tetanic stimulation on the twitch responses of the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum was investigated. In the presence of naloxone plus indomethacin twitch contractions following tetanus were potentiated. This posttetanic potentiation (PTP) of twitches was absent after reducing calcium concentration (0.6 mmol/l) in the bath or lowering bath temperature (22 degrees C); doubling calcium concentration (5 mmol/l) enhanced PTP. The addition of ouabain (0.8-5 mumol/l) prevented PTP; following the washout of ouabain the time course of PTP was prolonged. Hexamethonium (0.5 mmol/l) did not prevent PTP. The results suggest that similarly to the situation at nicotinic synapses of the striated muscle the mechanism of PTP at this muscarinic synapse might be associated with changes in calcium distribution. Moreover, the effect of ouabain might suggest the importance of electrogenic sodium pumping from and hyperpolarization of cholinergic nerve terminals after tetanus.

Animals↗
PubMed1982

The analysis of post-tetanic potentiation in guinea-pig ileum longitudinal muscle strip.

The effect of tetanus on the twitch responses of the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum to electrical stimuli was investigated in the presence of naloxone and indomethacin. Naloxone was used to prevent post-tetanic twitch inhibition due to the release of endogenous opiate ligands, and indomethacin to diminish pretetanic twitch height. Twitch contractions following tetanus were potentiated in the presence of both drugs. The optimal stimulation parameters for the manifestation of post-tetanic potentiation (PTP) were determined; tetanic stimulation: 30 Hz for 25 s. supramaximal impulse intensity; twitches: 0.04 Hz, low impulse intensity. PTP was also obtained when indomethacin was replaced by noradrenaline or adenosine, i.e. by drugs whose mechanism of action also includes a presynaptic effect. Postsynaptic changes in contractility cannot fully account for the observed PTP of twitches judging from the smaller effect of tetanus on acetylcholine-evoked contractions. The hypothesis of a presynaptic origin of PTP at this muscarinic synapse was corroborated in the experiments where acetylcholine stores were labelled with [3H] choline and the release of the label was increased during PTP. Furthermore, a bioassay showed that the output of endogenous acetylcholine in the post-tetanic interval was increased in the presence of naloxone plus indomethacin but not in their absence. The fact that PTP was also observed in the absence of any drug, if the tetanic stimulation was short (10 s) and of low impulse intensity, suggested its possible physiological significance.

Acetylcholine↗
PubMed1981

Mutual connections of the raphe system and hypothalamus in relation to fever.

Previous studies in our laboratory have shown that lesions in certain brain stem regions prevent elevations of body temperature after administration of bacterial pyrogen. In the present experiments wer examined the morphology of the connections of these "brain stem thermoregulatory centers" which are represented in all raphe and paraphe nuclei of the brain stem reticular formation. The methods of anterograde degeneration and tracing of retrograde transport of horseradish peroxidase were used to identify afferent and efferent connections within this "thermoregulatory field." Abundant mutual connections between the raphe nuclei and hypothalamus were found. All nuclei of the raphe system receive afferents from the medial and lateral hypothalamus. All raphe nuclei have efferent projections to the medial reticular formation, and the raphe nuclei of the pons and mesencephalon provide ascending fibers to the hypothalamus. A lesion of any part (origin, course, termination field) of this mutual raphe-hypothalamic pathway system will prevent development of fever in response to bacterial pyrogen.

Animals↗
PubMed1981

Drug effects on attack defense and escape in mice.

The relative specificity and potency of action of 32 neuropsychotropic drugs was assessed on attacks, defensive upright postures and escapes occurring in singly-housed male mice during interactions with non-aggressive strange males. Scopolamine was most potent in reducing attacks while apomorphine was most active in stimulating attacks. Defenses and escapes were inhibited most efficiently by pentobarbital and diazepam, while L-tryptophan was most active of the tested drugs in stimulating defenses and escapes. Aminooxyacetic acid and valproate inhibited both attack and defensive-escape behavior at relatively low doses. Inhibition of attacks by many drugs tested could be explained by anticholinergic, serotonergic or gabaergic effects while stimulation of attacks may be due to dopaminergic effects. Gabaergic drug actions seem to inhibit while serotonergic effects might stimulate defenses and escapes.

Aggression↗
PubMed1980

Central pyrogenic activity of muramyl dipeptide.

Fever can be elicited in the rabbit by the intravenous administration of relatively large doses of a synthetic immunoadjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP). This response could be mediated by endogenous pyrogen because MDP has been shown to induce their production both in vivo and in vitro. The results reported here show that intracisternal injection of minute amounts of MDP could elevate fever without activating the release of endogenous pyrogen in the plasma or in the cerebrospinal fluid. Moreover, indomethacin inhibited hyperthermia produced by intracerebroventricular administration of MDP. Therefore, our findings argue in favor of a direct effect of the glycopeptide on the thermoregulatory centers besides its indirect effect through the production of leukocytic pyrogen. This molecule apparently represents the minimal requirement for the pyrogenicity of bacterial peptidoglycan because administration, even by the intracerebral route, of a mixture of muramic acid and of its dipeptide moiety did not elicit fever.

Acetylmuramyl-Alanyl-Isoglutamine↗