Monitoring acid-base and electrolyte disturbances in intensive care.
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Biomedical subjects
Publications and source records attributed to K Masek.
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The administration of muramyl dipeptide (MDP) in a single dose of 2 mg/kg increased markedly the utilization of 3H-thymidine for the synthesis of DNA thymine in liver, kidney and thymus, while no effect has been observed in spleen. Higher doses of MDP (5 mg and 10 mg) did not further increase the effect, but, on the contrary, in some tissues such as thymus, the effect was abolished. The repeated administration of 1 mg/kg of MDP for 7 days, contrary to single administration, had no effects. The measurement of proliferation activity in the experiment where DNA in the organs has been previously labeled with 3H-thymidine, has shown that the repeated administration of MDP (1 mg/kg) led to a more rapid decay in specific activity of DNA thymine in liver, kidney and thymus, but no effect was seen in spleen. The activities of thymidine kinase in the cytosole fraction of thymus and spleen after a single administration of MDP (1 mg/kg), are influenced in different ways. While in thymus the enzyme activity increased between 16 and 24 h, not being markedly changed in the early intervals, in spleen a significant decrease in phosphorylation of 14C-thymidine can be observed as early as 2 h after administration, and the decrease persists up to 48 h.
The potency of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide, which have the immunoadjuvant and immunomodulatory activity on pain threshold was studied. Two different analgesiometric procedures were employed: hot plate test and acetic acid writhing test in mice and rats. Both compounds were injected intravenously (1-4 mg/kg), intraperitoneally (5-50 mg/kg) and intracerebroventricularly (0.5-4 mg/kg) and were able to produce mild transient analgesia in both species. Writhing response was more influenced after systemic administration of drugs while hot plate latencies was not. On the contrary, latencies in hot plate test were more affected than the writhing response after intracerebroventricular administration. Dose response curve showed a bell shaped feature typical for peptides. Pretreatment with naltrexone, an opiate antagonist, did not prevent the analgesic action of tested compounds. The hyperalgesia induced by administration of parachlorophenylalanine, a serotonin depletor, could be prevented by administration of a nonanalgesic dose of MDP (0.025 mg/kg). At higher dosages (1 mg/kg) MDP was able to antagonize also general toxic effects of pCPA. These results support the possibility of participation of central serotonergic structures in MDP and AdDP induced analgesia. The peripheral mechanism of action, however, can not be completely ruled out.
The pharmacology of cholinergic neurogenic responses evoked by the participation of only the endings of axon terminals was compared to that of responses evoked by participation of the more proximal parts of the terminals also. Myenteric plexus-longitudinal muscle strips of the guinea-pig ileum were drawn through narrow orifices in 2 rubber membranes dividing a bath into 3 separate compartments. Oral segments were stimulated electrically by single impulses or by trains and local neurogenic contractions were evoked. The contractions of the aboral segment due to nerve impulses transmitted from the oral segment via the middle segment were also recorded. The opioid ligands ketocyclazocine and [D-Ala2,MePhe4,Met(O)5-ol]enkephalin and noradrenaline inhibited the twitches of the aboral segment evoked by oral segment stimulation more than the local twitches of the oral segment when these agents were applied directly to the respective compartments. The twitches of the aboral segment were also inhibited by the application of these drugs into the middle compartment adjusted to 10 mm width. Verapamil and the alkaline earth metal ions cobalt and lanthanum had similar effects. 4-Aminopyridine increased twitch amplitude more in the aboral segment than in the oral segment when applied directly; similar effects in the aboral segment were seen when the agents were applied to the middle compartment. The action of atropine, papaverine, d-tubocurarine and prostigmine did not discriminate between twitches in the oral and aboral segment when applied directly and all drugs except prostigmine were without effect when applied to the middle compartment.(ABSTRACT TRUNCATED AT 250 WORDS)
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Output of acetylcholine (ACh), neurogenic electromyogram (NEMG) and contractions of guinea-pig ileum preparations were studied during stimulation by high-frequency trains of impulses. Under control conditions the output of ACh per impulse after 2nd to 4th impulses during train stimulation (30 Hz) was higher by 20-40% than the level of ACh output during the first impulse. In the presence of ketocyclazocine (KTZ, 80 nmol x l-1) the output of ACh evoked by the first impulse was more effectively inhibited than that after impulses 2 to 4 so that the increase was higher (80-170%). NEMG, a direct consequence of the localized action of released transmitter (ACh), was recorded in the longitudinal muscle 4 and 10 mm aborally from the focal stimulation site. The incidence of NEMG responses was higher at the proximal than at the distal site and was proportional to the number of impulses in a train (100 Hz). At the distal site KTZ suppressed the appearance of NEMG responses to single impulses whereas at the proximal site its effect was much less; and so was its effect at either site during train stimulation. It is concluded that in the course of train stimulation, sites of transmission more distant from the stimulation focus were recruited, and consequently the secretion of ACh in succeeding impulses was enhanced. KTZ might preferentially inhibit the propagation of excitation by the very first impulse.
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Output of acetylcholine (ACh), electromyogram (EMG) recordings and contractions of myenteric plexus-longitudinal muscle strip preparations from the guinea-pig ileum were studied during stimulation by single impulses or by trains (30 Hz; 2 to 128 impulses) under control conditions and in the presence of noradrenaline (NA). During supramaximal stimulation NA (2.5 microM) inhibited both contractions of the smooth muscle and the release of ACh evoked by single impulses more effectively than those evoked by train stimulation so that in a train of 4 impulses the output of ACh per impulse after the 2nd to 4th impulses was 69 to 104% higher than the output after the 1st impulse. During submaximal stimulation, contractions and ACh release evoked by single impulses were almost completely inhibited by NA. The neurogenic EMG, a direct consequence of the localized action of released transmitter (ACh), was recorded in the longitudinal muscle 4 and 10 mm aborally from the focal stimulation site. The incidence of the neurogenic response was much higher at the proximal (4 mm) than at the distal (10 mm) site and was proportional to the number of impulses in a train (100 Hz). NA inhibited propagation of the neurogenic response evoked by single impulses whereas its effect during train stimulation was less. It is concluded that in the course of train stimulation, sites of transmission more distant from the stimulation focus was recruited, and consequently the secretion of ACh in succeeding impulses was enhanced. NA could interfere with this process; it might inhibit the invasion by action potentials of cholinergic nerve terminal varicosities, thereby reducing the release of ACh.
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Serotoninergic contractions of the rat stomach strip were evoked and EC50 determined. In preparations from control animals MDP, 50 mumol/l, decreased EC50 or sensitized the preparation. In the strips from animals where adjuvant arthritis was induced, higher sensitivity to 5-HT was observed and the sensitizing effect of MDP was retained. In the strips from animals pretreated with cyclophosphamide or in the terminal stage of tumor growth lower sensitivity to 5-HT, which could be further decreased by MDP, were noticed. These opposite effects in serotoninergic reactions were tentatively linked with the modulation of the immune status in vivo.
The effect of intravenous administration of a nonpyrogenic (25 micrograms/kg) and pyrogenic (2000 micrograms/kg) dose of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) on sleep stages was tested. During the daytime study neither dose changed slow wave sleep. Rapid eye movement sleep was influenced, however, depending on the dose used. Small doses of MDP significantly increased and high doses decreased REM sleep. During the dark phase of the day (evening study) administration of 25 micrograms/kg of MDP caused enhancement of both slow wave sleep and REM sleep.
Three different approaches were utilized for illustration of membranous effect of muramyl dipeptide (MDP) on liver cells. Toxicologic approach using a hepatoprotective effect against CCL4 as well as from previous results with other toxins. Histochemistry and microfluorometry after chemical injury. Biochemical as assessed by modulation of 14C palmitic acid incorporation under MDP effects in neutral lipids and phospholipids content of cell membranes. By this integrated study we may assume MDP played a role in one or more cell membrane(s). This assumption was supported by reduction of hepatocyte injury as assessed by enzyme analysis in serum or in the cells. Moreover, MDP pretreatment influenced the increase in the incorporation of labeled palmitic acid in neutral lipids and phospholipids. Microscopical image analysis and histochemical results supported the aforementioned findings.
Muramyl dipeptide (MDP) and a number of synthetic analogs, until very recently considered to be important mainly for their immunomodulatory activity, have been investigated. Papers dealing with these properties of MDP have been reviewed (1,2).