Biomedical subjects

F Mori

Publications and source records attributed to F Mori.

At least 19 recordsLinked to original sources

PubMed1992

Thiokynurenates prevent excitotoxic neuronal death in vitro and in vivo by acting as glycine antagonists and as inhibitors of lipid peroxidation.

Several derivatives of kynurenic and thiokynurenic acids were synthesized and tested for their ability to protect primary cultures of cerebellar granule cells against excitotoxic damage, and to affect the binding of [3H]glycine ([3H]Gly), [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA), [3H]3-(2-carboxypiperazine-4-yl-)propyl-1-phosphonic acid ([3H]CPP), [3H]kainic acid and [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical membranes. Kynurenic and thiokynurenic acid derivatives with one or two halogens in position 5 or 7 were selective glycine antagonists, failing to affect N-methyl-D-aspartate (NMDA), kainate or AMPA sites at micromolar concentrations. 7-Cl-kynurenic, 7-Cl-thiokynurenic, 5,7-diCl-kynurenic and 5,7-diCl-thiokynurenic acids had similar IC50s for displacing [3H]Gly from its strychnine-insensitive site and for reducing the stimulated (0.5 microM NMDA and 1 microM glycine) [3H]TCP binding to cortical membranes. However, 7-Cl-thiokynurenic acid was particularly potent to prevent excitotoxic neuronal death in cultured cerebellar granule cells. This action may be ascribed to inhibition of lipid peroxidation, a property which was demonstrated for the 5- or 7-Cl derivatives of thiokynurenic acid. Furthermore, 7-Cl-thiokynurenic acid reduced excitotoxic damage caused by the injection of quinolinic acid in the rat striatum. Thus, 7-Cl-thiokynurenic acid appears to be a new compound with interesting antiexcitotoxic properties both in vitro and in vivo.

Animals↗

PubMed1992

In vitro protection of acetylcholinesterase and butyrylcholinesterase by tetrahydroaminoacridine. Comparison with physostigmine.

The protective action of 1,2,3,4-tetrahydro-9-aminoacridine (THA) against the long-lasting inactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) brought about by diisopropylfluorophosphate (DFP) and physostigmine, as well as by neostigmine in the case of AChE only, was evaluated by a dilution technique using Electrophorus electricus AChE and horse serum BuChE as target enzymes. In parallel experiments, the ability of physostigmine itself to protect these enzymes from DFP was evaluated and compared with that of THA. THA pretreatment was seen to prevent in a dose-dependent manner the inhibition of both AChE and BuChE. However, it was appreciably more potent towards AChE than towards BuChE. THA mean EC50 values for protecting AChE against 10, 40 and 100 microM DFP were 0.04, 0.16 and 0.45 microM, respectively; against 1 microM physostigmine the value was 1.8 microM and against 1.2 microM neostigmine it was 3.0 microM. The THA mean EC50 value for protecting BuChE against 3 microM physostigmine was 0.55 microM and the values for protecting against 3, 10 and 40 microM DFP were 1.5, 3 and greater than 10 microM, respectively. The protective action of THA was time independent: recovery of the maximal enzymic activity was immediate upon dilution. Unlike THA, the protective action of physostigmine developed progressively after dilution and was maximal within 3-4 (AChE) or 6-8 hr (BuChE). Under our experimental conditions, 0.3 microM physostigmine protected approximately 70% of AChE from 40 microM DFP and 5 microM physostigmine protected 9 and 47% of BuChE from 40 and 3 microM DFP, respectively. The results of this work suggest that THA exerts its protective action by shielding the active site of AChE and BuChE from the attack of the inactivating agents on account of its higher enzymic affinity, whereas the protective action of physostigmine against DFP takes advantage also of the carbamylation of the enzyme. These results are in line with the hypothesis that protection of AChE is the primary mechanism responsible for the antidotal action of THA against organophosphorus poisoning.

Acetylcholinesterase↗

PubMed1992

[A new hemodynamic diagram, using COP-PCWP and CI as parameters, after open heart surgery].

In 24 patients subjected to cardio-pulmonary bypass (CPB) operation, changes in colloid oncotic pressure (COP), cardiac index (CI), respiratory index (RI), and pulmonary capillary wedge pressure (PCWP) were measured within a 48 hour period. The patients were divided into two groups according to dose levels of catecholamine. In 18 patients received small catecholamine doses, a stable hemodynamic and respiratory status were maintained. However, 6 patients received catecholamine doses of more than 15 micrograms/kg/min exhibited low COP, low CI, high RI and high PCWP. In this study we designed a new hemodynamic diagram using COP-PCWP and CI as parameters of the cardiac function. We consider that these parameters are more suitable than Forrester's parameters to evaluate the patient's condition before and after open heart surgery.

Adult↗

PubMed1991

Thiokynurenates: a new group of antagonists of the glycine modulatory site of the NMDA receptor.

Several substituted derivatives of kynurenic acid were tested on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex present in the guinea pig myenteric plexus, on the binding of [3H]glycine and of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) to rat cortical membranes and on the depolarization of mice cortical wedges induced by NMDA or quisqualic acid (QA). Kynurenic acid derivatives, having a chlorine (CI) or a fluorine atom in position 5 or 7 but not in position 6 or 8 had significantly lower IC50s than the parent compound when tested on the antagonism of glutamate-induced ileal contraction and in the glycine binding assay. A further significant increase in potency was obtained by substituting a thio group for the hydroxy group in position 4 of kynurenic acid: the IC50 was 160 +/- 20 microM of kynurenic acid and 70 +/- 15 microM of thiokynurenic acid in the myenteric plexus whereas these IC50s for glycine binding were 25 +/- 3 and 9 +/- 2 microM respectively. Several thiokynurenic acid derivatives were synthetized and showed an increased affinity for the glycine recognition site over the corresponding kynurenic acid derivatives. Glycine competitively antagonized the actions of the thiokynurenates in the ileum, in cortical wedges and on [3H]TCP binding. In this preparation, 7-Cl-thiokynurenic acid had an IC50 of 8 microM for antagonizing 10 microM NMDA-induced depolarization while 50% of the 10 microM QA depolarization was antagonized at 300 microM. Thus thiokynurenic acid derivatives seem to be a new group of potent and selective antagonists of strychnine-insensitive glycine receptors.

Animals↗

PubMed1991

Effectiveness of 1,2,3,4-tetrahydro-9-aminoacridine (THA) as a pretreatment drug for protection of mice from acute diisopropylfluorophosphate (DFP) intoxication.

The protective action of 1,2,3,4-tetrahydro-9-aminoacridine (THA) against acute diisopropylfluorophosphate (DFP) intoxication was evaluated in mice by measuring the effects of the pretreatment of the animals with various doses of the drug on the DFP LD50. In the same experiments, the action of physostigmine and pyridostigmine were compared. THA at the doses 2.5, 5 and 7.5 mg/kg injected subcutaneously 15 min before DFP caused a dose-dependent increase in the DFP LD50, resulting in protection ratios equal to 3, 3.1 and 4.4, respectively, in the absence of atropine and 4.5, 8.6 and 14.5, respectively, in the absence of atropine and 4.5, 8.6 and 14.5, respectively, in the presence of atropine sulfate (17.4 mg/kg) therapy. Under the same experimental conditions, the protective ratios of 0.1 mg/kg physostigmine and pyridostigmine were 2.2 and 1.3, respectively, without atropine and 11.0 and 12.2, respectively, with atropine. The effectiveness of THA antidotal effect was inversely correlated to the time between pretreatment and DFP administration, being maximal when THA was injected 15 min before poisoning. In separate experiments, the time-course of acetylcholinesterase (AChE; EC 3.1.1.7) activity recovery was evaluated in the whole brain and diaphragm tissues of mice pretreated with THA (5 mg/kg) and physostigmine (0.1 mg/kg) 15 min before poisoning with DFP (8 mg/kg). At 10 min after DFP administration residual AChE activity in the brain averaged 4, 25 and 15% of that in controls in the animals pretreated with atropine alone, atropine plus THA or atropine plus physostigmine, respectively. At 24 h after poisoning, brain AChE activity averaged 34 and 47% of that in controls in the mice protected by THA and physostigmine, respectively. As for the diaphragm, AChE activity in THA-pretreated animals was 29% of controls 10 min after poisoning versus 8 and 23% in unprotected and physostigmine-pretreated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Evaluation of a new calcium containing cardioplegic solution in the isolated rabbit heart in comparison to a calcium-free, low sodium solution.

Isolated perfused rabbit hearts were studied to compare the effects of 3 hour ischemic arrest following either calcium-free or calcium-containing cardioplegia, on the recovery of isovolumic function of the left ventricle, coronary flow, release of creatine phosphokinase and myocardial water content. The hearts perfused with the calcium-containing solution (Ca 0.5 mmol/L) showed better recovery of the developed pressure in the left ventricle, and its first derivative and compliance. Coronary flow at a constant perfusion pressure was better restored during reperfusion in the hearts with calcium-containing solution. The release of less CPK and a lower water content were also observed in the hearts reperfused with calcium-containing solution. We concluded that calcium-containing cardioplegic solution with a high concentration of magnesium (10 mmol/L) was superior to calcium-free solution for myocardial protection.

Animals↗

PubMed1991

Pathological studies on central nervous tissues of rats infected with Rattus serotype hantavirus (SR-11 strain).

Newborn rats inoculated intraperitoneally with a hantavirus strain (SR-11) developed neurological signs such as ataxia and limb paralysis. The main histological lesions were scattered and multiple neuronal degeneration and necrosis with eosinophilic cytoplasmic inclusion bodies (CIB) in the brain, spinal cord and ganglia. Immunohistochemically, the viral antigen was detected in neurons, capillary endothelial and glial cells throughout the nervous tissue and CIB were identified as consisting of hantaviral antigen (nucleocapsid protein). Ultrastructurally, CIB in the neurons consisted of an accumulation of granular or filamentous materials, or both. They were seen near a well-developed Golgi apparatus and associated with well-developed rough endoplasmic reticulum and increased numbers of ribosomes. The present results suggested that this virus strain was highly infective in neurons of the newborn rats and that excess production of viral antigen which accumulated as CIB resulted in the neuronal changes.

Animals↗

PubMed1991

Protection of acetylcholinesterase by meptazinol in mice exposed to di-isopropyl fluorophosphate. Comparison with physostigmine.

The protective action of meptazinol against acute di-isopropyl fluorophosphate (DFP) intoxication has been evaluated in mice by measuring the effects on the DFP LD50 of the pretreatment of the animals with increasing doses of the drug. Meptazinol at the doses 15, 30 and 45 mg kg-1 injected 15 min before DFP caused a dose-dependent increase in the DFP LD50, resulting in protection ratios equal to 2.1, 4.8 and 9.7, respectively, in the absence of atropine and 2.5, 4.7, and 8, respectively, in the presence of atropine sulphate (17.4 mg kg-1) therapy. Under the same experimental conditions, the protective ratio of 0.1 mg kg-1 physostigmine sulphate was 2.2 and 7.3 in the absence and presence of atropine therapy, respectively. In separate experiments, the time course of acetylcholinesterase (AChE) activity recovery was evaluated in the brain and diaphragm of mice pretreated with meptazinol (30 mg kg-1) or physostigmine (0.1 mg kg-1) 15 min before poisoning with DFP (8 mg kg-1). Ten minutes after poisoning, residual AChE activity in the brain averaged 4, 47 and 15% of that in controls in animals pretreated with atropine alone, atropine plus meptazinol or atropine plus physostigmine, respectively. Twenty four hours after poisoning, brain AChE activity averaged 31 and 47% of that in controls in mice protected by meptazinol and physostigmine, respectively. The data from the diaphragm closely paralleled those from the brain. It is concluded that high doses of meptazinol exert antidotal action against acute DFP poisoning in the mouse comparable in efficacy with that of physostigmine combined with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1991

[Chylothorax developed after cardiac surgery in children: a report of three cases].

Two children developed chylothorax after median sternotomy and a third child developed chylothorax after a Blalock-Taussig operation under the left thoracotomy. The first patient had a closure of ASD and a pulmonary valvotomy and then later developed chylothorax. The thoracic duct was ligated 10 cm just above the diaphragm at 28 days after the first operation because of unsuccessful conservative treatment. The second patient had a Blalock-Taussig operation and the third patient had radical operation for ECD and both developed chylothorax. The latter two patients were cured with conservative treatments such as the administration of Medium Chain Triglyceride or total parenteral nutrition with thoracic drainage. Children who developed chylothorax after cardiac surgery should be treated conservatively for at least the early postoperative period when circulatory and/or respiratory conditions are still unstable.

Child, Preschool↗

PubMed1991

[Centrifugal pump as right ventricular assist pump in the treatment of right ventricular failure following resection of left atrial myxoma].

A 31-year-old woman had a left atrial myxoma associated with severe pulmonary hypertension and respiratory failure because of incarceration of the tumor to the mitral valve. Emergency surgery was performed, but the patient could not be weaned from cardiopulmonary bypass because of right ventricular failure. A Biomedicus centrifugal pump was used as a right ventricular assist pump. The result was a successful termination of cardiopulmonary bypass. With the support of an intra-aortic balloon pump, the right ventricular assist pump was removed 38 hours after the operation, and the intra-aortic balloon pump was terminated 2 days later. The centrifugal pump is very useful at the majority of centers where the pneumatically activated bi-valved ventricular assist device is unavailable. The Biomedicus centrifugal pump can be easily applied for treatment of perioperative right ventricular failure and is very useful for short-term use without systemic anticoagulants.

Adult↗

PubMed1990

Chemical composition, particle size range, and biological activity of some low molecular weight heparin derivatives.

Several low molecular weight (LMW) heparin sodium derivatives from different sources, as well as some related regular heparin sodium preparations, were examined for chemical composition by high field (300 MHz) 1H NMR spectroscopy, for particle size range by quasi-elastic light scattering (QELS) methods, and for anti-coagulation potency and anti-factor Xa activity by the standard U.S. Pharmacopeial assays described for regular heparin. The NMR spectra provided insight into possible modes of depolymerization used to generate the LMW heparins, as well as into the presence of dermatan sulfate or other chemical contaminants. The QELS analysis permitted the heparin preparations to be characterized and compared by virtue of their distinctive particle size distributions.

Dermatan Sulfate↗

PubMed1990

The effect of the left ventricular assist device on the myocardium during reperfusion after coronary artery occlusion.

The effect of the left ventricular assist device (LVAD) during reperfusion after acute coronary occlusion was evaluated in a canine experimental model. The left circumflex artery was occluded for one hour, then reperfused for six hours immediately after removal of the occluder. Sixteen mongrel dogs were divided into the following two groups; a control group comprised of 7 dogs not given the LVAD support and another group comprised of 9 dogs (the LVAD group) assisted by LVAD for five hours during reperfusion. Throughout the study period, there was no significant difference in heart rate, aortic pressure or PA pressure between the two groups. However, LA pressure was significantly lower, while cardiac output, LV dp/dt, and LVSW were significantly higher in the LVAD group compared to the control group. Regional myocardial blood flow in the LCx area was significantly decreased after LCx occlusion in both groups but in the LVAD group, it recovered to the same level as before LCx occlusion after the beginning of reperfusion, while in the control group it remained significantly low throughout reperfusion. The LVAD group showed a positive myocardial lactate extraction in the early reperfusion period however, there was persistent lactate production in the control group. Thus, the unloading effect of LVAD during reperfusion after acute coronary artery occlusion improved regional myocardial blood flow and myocardial lactate metabolism and consequently, left ventricular function showed better recovery even after weaning from the LVAD support.

Animals↗

PubMed1990

Effect of combined dopamine and bunazosin on the ischemic heart after occlusion of the coronary artery.

In order to investigate whether dopamine combined with bunazosin improves cardiac function, the global and regional cardiac function and regional blood flow of 7 anesthetized dogs were analyzed before and after occlusion of the left anterior descending coronary artery (LAD), then after 10 micrograms/kg/min dopamine infusion following the LAD occlusion, and again after a bolus infusion of bunazosin 250 micrograms/kg. Dopamine with bunazosin reduced left atrial pressure from 4.9 +/- 0.9 to 3.1 +/- 0.5 mmHg (p less than 0.05) and improved cardiac output from 1.22 +/- 0.15 to 1.50 +/- 0.14 L/min (p less than 0.05), maximum positive left ventricular dp/dt from 1721 +/- 202 to 3600 +/- 663 mmHg/sec (p less than 0.05) and the time constant from 45.2 +/- 5.0 to 27.5 +/- 4.6 msec (p less than 0.01). Bunazosin added to the dopamine reduced the elevated left ventricular peak systolic pressure caused by dopamine from 130 +/- 7 to 113 +/- 8 mmHg (p less than 0.01). With regard to the regional wall motion, the impaired LAD-delta L (the segment systolic shortening) and LAD-Elmax (the slope of peak systolic pressure--endsystolic length relation) following the LAD occlusion improved from 0.5 +/- 2.5 per cent to 5.9 +/- 2.6 per cent (p less than 0.01) and from 50 +/- 9 to 82 +/- 14 mmHg/mm (p less than 0.01) after the infusion of dopamine with bunazosin. Dopamine greatly increased the Rate Pressure Product (RPP) from 12610 +/- 1120 after LAD occlusion to 16950 +/- 1420, whereas dopamine in combination with bunazosin did not increase the RPP due to a drop of LV-PSP with little change in regional myocardial blood flow. It was concluded that combining dopamine with bunazosin was useful for improving both the global and regional cardiac functions of the ischemic heart.

Adrenergic alpha-Antagonists↗

PubMed1990

Clinical trial of nicardipine cardioplegia in pediatric cardiac surgery.

To clarify the effectiveness of nicardipine, one of the dihydropyridine calcium-channel blockers, for myocardial protection during cold potassium cardioplegic arrest in pediatric cardiac surgery, a clinical trial of nicardipine (0.25 mg/L) added to potassium cardioplegic solution was performed in children undergoing surgical repair of congenital heart diseases. Twenty patients were selected to receive nicardipine cardioplegia and 13 patients received a standard potassium cardioplegia, serving as a control group. Nicardipine cardioplegia provided better cardiac performance in the early postoperative period and reduced release of the MB isozyme of creatine kinase, as determined during a 48-hour postoperative period. These results suggest that nicardipine added to cold potassium cardioplegic solution offers additional protection for the myocardium during ischemia and postischemic reperfusion in pediatric cardiac surgery.

Blood Pressure↗

PubMed1990

Glycine-related amino acids stereoselectively affect N-methyl-D-aspartate receptor-mediated contractions of guinea pig ileum: comparison with the inhibition of strychnine-insensitive [3H]glycine binding to rat cortical membranes.

Ten microM glycine, D-serine and D-alanine potentiated L-glutamate (30 microM)-induced contractions of the guinea pig ileum by an average of 35, 53 and 24%, respectively. On the contrary, D-cysteine, at the same concentration, caused a 21% inhibition of the contractile response to L-glutamate. This inhibitory effect of D-cysteine was abolished by 10 microM glycine. The corresponding L-isomers of these amino acids, namely L-serine, L-alanine and L-cysteine and the other amino acids tested, possessed negligible activity or were inactive in this test. The IC50 values of the same compounds for strychnine-insensitive binding of [3H]glycine (20 nM) to cortical membranes from the brain of the rat were: 0.26 microM, glycine; 1.2 microM, D-serine; 2.1 microM, D-alanine; 8.6 microM, D-cysteine; 51 microM, L-serine; 90 microM, L-alanine; greater than 1000 microM, L-cysteine. On the whole, these results point out a strict requirement for stereoselectivity for both of the effects examined. In addition, the results obtained in the ileum preparation suggest that D-cysteine may act as an antagonist, rather than as an agonist at the glycine site which regulates the responses of N-methyl-D-aspartate receptors.

Amino Acids↗

PubMed1990

[Evaluation with Doppler echocardiography of the Bjork-Shiley Monostrut prosthesis in the mitral position].

The Doppler characteristics of Björk-Shiley Monostrut prostheses in mitral position were studied in 53 patients (35 women; 18 men; mean age 53.8 yrs). Valvular function was considered normal on the basis of clinical and echocardiographic evaluation. Mean follow-up after surgery was 23.9 +/- 12.0 months (range 9-53). M-mode, two-dimensional and colour flow mapping echo were performed in each patient. Transvalvular blood flow characteristics were examined by colour flow imaging whereas peak and mean gradient through the valve, pressure half-time and prosthetic area were calculated using continuous wave Doppler. In 84% of patients, colour flow mapping showed a transprosthetic flow with 2 jets; in 78% the jets were different: the main one was directed towards the free wall of left ventricle in 52% and towards the interventricular septum in 48%. Thus, the main jet direction was dependent on the spatial position of the prostheses and the orientation of the disc. In 16% a single jet flow was present during the whole diastole. CW Doppler showed the following parameters: peak velocity 1.6 +/- 0.3 m/s; peak gradient 10.7 +/- 3.9 mmHg; mean gradient 3.8 +/- 2.3 mmHg; pressure half-time 83.3 +/- 16.6 msec; prosthetic area 2.7 +/- 0.51 cm2. No statistically significant difference was found between different size prostheses. Our data show the excellent long term hemodynamic parameters of Björk-Shiley Monostrut mitral prosthesis and confirm the value of colour flow mapping in identifying normal transprosthetic flow profile.

Adult↗

PubMed1990

[Effects of hypertrophy on cardiac systolic and diastolic performance in athletes with mild hypertension].

Aims of the study has been the evaluation of morphological and functional aspects of left ventricle in subjects undergoing mild hypertension and sport adaptation effects. These evaluations have been carried out by Echo-Doppler both at rest and during sharp increase in after load induced by isometric stress. Together with the morphological parameters represented by mass index and by radius to thickness ratio, we have studied stroke volume and transmitral flow pattern assessing the maximum flow velocity during rapid filling phase (E), during atrial contraction phase (A) and their ratio (E/A). We have studied 31 male subjects from 39 to 60 (average 47) exercising twice or three times a week (in the main, aerobic sports such as road cycling). They were subdivided into two groups, the first included 16 subjects with mild hypertension (AP = 155 +/- 9/97 +/- 5 mmHg) the second included 15 normotensive subjects without known pathologies, comparable for age and body surface (AP = 125 +/- 15/77 +/- 10 mmHg). Hypertensive subjects exercising regularly, showed a mass index (164 +/- 42 g/m2) significantly higher than the controls (139 +/- 35 g/m2, P less than 0.01) but they ke a normal filling pattern at rest and similar stroke volume values. During isometric exercise instead, the velocities of E and A waves showed a different trend in the two groups with a higher reduction in E/A ratio in hypertensive subjects. The per cent decrease in this ratio turned out to be 15% in the control group and 33% in hypertensive subjects (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

[The effect of the co-existence of verapamil and residual propranolol on the left ventricular contractility].

The combined effect of the residual propranolol, which was administrated up to the coronary revasculization, and verapamil, anti-supraventricular tachycardia drug, on the left ventricular contractility was evaluated with left ventricular end-systolic pressure-diameter relationship. Methods; Eighteen sheep were instrumented with ultrasonic crystals on the anterior and posterior wall, endocardium and epicardium. A pressure transducer was placed in the left ventricle. Propranolol (0.15 mg/kg) (n = 6) or verapamil (0.15 mg/kg) (n = 6) or both drugs (n = 6) were administrated intravenously, and cardiac function was evaluated. Results; In combined group, end-systolic pressure-diameter ratio (Emax) was significantly decreased (2.95 +/- 0.24 mmHg/mm) as compared to the control group (7.95 +/- 0.83), propranolol group (6.27 +/- 0.78), and verapamil group (4.54 +/- 0.77). Conclusion; Co-existence of propranolol and verapamil significantly decreased cardiac contractility. Therefore verapamil should be administrated carefully in the presence of residual propranolol, and the co-existence of both drugs must be limited.

Animals↗