PubMed · 14913678
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1952. SPINAL anesthesia.. https://pubmed.ncbi.nlm.nih.gov/14913678/
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The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.
Amidated and nonamidated progastrin-derived peptides have distinct biological activities that are mediated by a range of receptor subtypes. The objective was to determine the nature of the stored and secreted progastrin-derived peptides and to investigate whether progastrin release is regulated by gastric acidity. Using an antiserum directed to the C terminus of progastrin for identification and to monitor purification, C-terminal flanking peptides (CTFP) of progastrin (prog(76-83), prog(77-83), and prog(78-83) in approximately equivalent amounts) were isolated and identified from extracts of sheep antrum using ion exchange, HPLC, and mass spectrometry. Only trace amounts of full-length progastrin were present. Progastrin CTFP was the predominant progastrin-derived peptide in the antrum [progastrin CTFP/gastrin amide (Gamide) = 3]. Similarly, progastrin CTFP was the major circulating form in the antral (CTFP, 710 +/- 62 pmol/liter; Gamide, 211 +/- 35 pmol/liter) and jugular (CTFP, 308 +/- 16 pmol/liter; gastrin amide, 32 +/- 3 pmol/liter) veins. Alteration of gastric acidity in sheep by iv infusion of a H/K-adenosine triphosphatase inhibitor or somatostatin or by intragastric infusion of HCl demonstrated that the CTFP concentrations changed, although to a lesser extent than the changes in circulating gastrin amide. We conclude that the CTFP of progastrin is the major stored and circulating species of the gastrin gene, and that it is secreted in a regulated fashion rather than constitutively. Because full-length progastrin is bioactive, but is only a minor antral and secreted form, determination of the biological activity of the C-terminal flanking peptides will be important for a complete understanding of gastrin endocrinology.
To clarify the jaw-closer and tongue-retractor muscle activity patterns during mastication, electromyographic activity of the styloglossus (SG) as a tongue-retractor and masseter (Mass) as a jaw-closer muscles as well as jaw-movement trajectories were recorded during cortically evoked rhythmic jaw movements (CRJMs) in anesthetized rabbits. The SG and Mass muscles were mainly active during the jaw-closing (Cl) phase. The SG activity was composed of two bursts in one masticatory cycle; one had its peak during the jaw-opening (Op) phase (SG1 burst) and the other during the Cl phase (SG2 burst). The Mass activity during the Cl phase was dominant on the working side (opposite to the stimulating side) while the SG1 and SG2 bursts were not different between the sides. When the wooden stick was inserted between the molar teeth on the working side during CRJMs, the facilitatory effects on the SG1 and SG2 bursts on both sides were noted as well as those on the Mass bursts, but the effects on the SG1 burst seemed to be weak as compared with those on the Mass and SG2 bursts. The difference in the burst timing between the sides was noted only in the SG1 burst. When the trigeminal nerves were blocked, the peak and area of the SG and Mass burst decreased during CRJMs, and the facilitatory effects of the wooden stick application on the muscles were not noted. The results suggest that the jaw and tongue muscle activities may be adjusted to chew the food and make the food bolus.