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F Mori

Publications and source records attributed to F Mori.

At least 91 records · Page 5Linked to original sources

[Early ocular changes in a tree shrew model of diabetes].

We developed a tree shrew model of diabetes using streptozotocin (STZ), and studied early ocular changes of diabetes (after one week of diabetes) by fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400 mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed diabetes. Corneal autofluorescence was significantly increased one week after STZ injection. These changes may be related to impairment of the ocular homeostatic mechanisms due to the onset of diabetes. Using this model, we might be able to obtain diabetic ocular impairment data closer to human data than in previous models of diabetes, because tree shrews are primates.

Animals↗

[Reproducibility of spasm in patients with long-term remission of vasospastic angina by medical treatment].

The reproducibility of coronary vasospasm was assessed in nine patients with complete remission of vasospastic angina by medical treatment by reexamination at intervals of mean [+/-SD] 5.7 +/- 0.9 years. Twenty-one segments were defined as spastic, demonstrating more than 90% narrowing after acetylcholine injection at the initial angiography. The degree of spasticity, type of spasm (diffuse or focal) and coronary artery diameter in these segments at the initial and follow-up studies were compared. Of the 21 segments, 17 (81%) still had some spasticity (> 25%) at the follow-up study and 8 (38%) of these 17 showed spasticity with greater than 90% narrowing. On the other hand, spasm was not reprovoked in 4 (19%) segments. Luminal diameter of the spastic segments decreased significantly at the follow-up study (2.52 +/- 0.83 vs 2.26 +/- 0.62 mm, p = 0.01), but percentage stenosis was not different between the initial and follow-up studies (9.1 +/- 7.2 vs 10.3 +/- 8.0%, NS). The reproducibility of the type of spasm provoked was 83%. Coronary vasospasticity persists to some extent in spite of complete remission of angina by medical treatment, and the type of spasm provoked has high reproducibility. Therefore, the cessation of drug treatment should be done carefully.

Acetylcholine↗

Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats.

PURPOSE: Elevation of diacylglycerol (DAG) and protein kinase C (PKC) levels in diabetic vascular tissue is associated with abnormalities of retinal and renal hemodynamics. The object of this study was to determine whether direct elevation of retinal DAG levels, in the absence of diabetes or hyperglycemia, can mimic the hemodynamic abnormalities normally observed in diabetic rats. Retinal DAG levels were elevated using an inhibitor of DAG kinase that converts DAG to phosphatidic acid. The effectiveness of a specific PKC-beta isoform inhibitor introduced directly into the retinas of diabetic rats in reversing diabetes-related abnormal retinal hemodynamics was also investigated. METHODS: For retinal blood flow studies, diacylglycerol kinase (DGK) inhibitor R59949, at various concentrations, was injected into the vitreous of nondiabetic Sprague-Dawley rats (n = 33), and a PKC-beta isoform-selective inhibitor LY333531 was injected into the vitreous of rats with streptozotocin (STZ)-induced diabetes of 2 weeks' duration (n = 21). Retinal hemodynamic changes were quantitated using video-based fluorescein angiography. Total DAG levels were assayed from five nondiabetic rat retinas after DGK inhibition and retinal PKC activities were assayed from six diabetic rat retinas after PKC-beta inhibition. RESULTS: DGK inhibitor R59949 injected into the vitreous dose dependently increased the mean circulation time (MCT) and decreased retinal blood flow (EC50 = 10(-8) M). After 30 minutes, 10(-5) M R59949 induced a 1.7-fold increase in total retinal DAG levels, compared with the levels in vehicle-injected eyes, an increase in MCT from 0.87 +/- 0.05 seconds to 1.44 +/- 0.12 seconds (P < 0.01) and a decrease in retinal blood flow from 105.3 +/- 6.5 pixel2/second to 64.1 +/- 5 pixel2/second (P < 0.01). The effect of R59949 was sustained for 60 minutes after injection. These retinal hemodynamic parameters after DGK inhibition were comparable to those measured at baseline in rats with STZ-induced diabetes of 2 weeks' duration (MCT = 1.38 +/- 0.20 seconds; retinal blood flow = 68 +/- 11.2 pixel2/second). Intravitreal injection of the PKC-beta inhibitor (LY333531) at 10(-5) M in diabetic rats decreased by a factor of 1.6 the diabetes-related increased PKC activation, decreased the prolonged MCT (0.98 +/- 0.13 seconds; P < 0.01) and increased retinal blood flow (93.4 +/- 14.2 pixel2/second; P < 0.01). The measured retinal circulatory parameters after PKC inhibition in the retina were comparable to those measured at baseline in the nondiabetic rats. CONCLUSIONS: These results provide direct evidence that DAG elevation and subsequent PKC-beta isoform activation are the primary biochemical sequelae responsible for the development of the abnormal retinal hemodynamics observed in diabetic rats.

Animals↗

The effect of cholinesterase inhibitors on the secretion of APPS from rat brain cortex.

In this study we examined the question whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat following electrical as well as pharmacological stimulation with bethanechol (BETHA). Three ChEI, both reversible and irreversible were tested for their ability to enhance the release of non-amyloidogenic soluble derivatives (APPs). These included physostigmine (PHY), heptyl-physostigmine (HEP) and 2,2-dichlorovinyldimethyl phosphate (DDVP), at the concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with BETHA. Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that long-term administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing and decreasing the formation of amyloidogenic APP products.

Amyloid beta-Protein Precursor↗

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle.

We encountered a rare case of combined intrauterine and extrauterine pregnancy that occurred following separate spontaneous ovulations. A 33 year old woman visited our hospital with the chief complaint of abdominal pain on April 16, 1993. Her last menstruation was from March 23 for 6 days. However, the urinary human chorionic gonadotrophin (HCG) on April 19 was 1024 IU/l. Pelvic examination and ultrasonography indicated an extrauterine pregnancy, which was confirmed by laparotomy and histological identification of trophoblast cells. The urinary HCG concentration markedly decreased after the operation. However, the HCG level increased again on the fifth post-operative day, and a gestational sac (11 mm) was identified in the uterine cavity on the 11th post-operative day, indicating that this intrauterine pregnancy was established following spontaneous ovulation which occurred before the removal of the extrauterine pregnancy. This case indicates that a combined pregnancy can occur not only after simultaneous multiple ovulations but also after the separate spontaneous ovulations.

Adult↗

Acetylcholinesterase inhibition and protection by dizocilpine (MK-801) enantiomers.

The optical isomers of the N-methyl-D-aspartate (NMDA) receptor ion-channel blocker dizocilpine (MK-801) were shown to interact with electric eel and rat brain acetylcholinesterase (AChE) in a mixed competitive-noncompetitive way. The (-) form, pharmacologically less active, was the most potent of the two isomers as an AChE inhibitor (Ki for electric eel and rat brain AChE being 6.2 and 17.9 microM, respectively, compared with 200 and 450 microM, respectively, of the (+) form). Both enantiomers premixed with AChE preparations, dose-dependently protected the enzyme from inactivation by diisopropylfluorophosphate (DFP). The maximal protective effects against 40 and 10 microM DFP were in the ranges 10.7-23.8 and 19.5-31.4% of control enzymic activity for the (+) and (-) forms of dizocilpine, respectively. The extent of the protective effect against DFP was increased up to 80.1% of control enzymic activity for (-)-dizocilpine and to 38.4% for (+)-dizocilpine by diluting the enzymic mixtures 1000 times after treatment with the organophosphate agent. The two enantiomers added to AChE 15 min after DFP, failed to reactivate the enzyme. Finally, it was shown that (+)- and (-)-dizocilpine dose-dependently and competitively decreased the DFP bimolecular reaction constant, K(i). We conclude that dizocilpine exerts a protective action towards AChE against irreversible DFP inhibition, but the molecular mechanism of such an action is at present unclear.

Animals↗

Lenticular autofluorescence in normal tree shrews.

Lenticular autofluorescence was measured in vivo in 25 normal tree shrews using a fluorophotometer with a specially designed small animal adapter to assess the usefulness of this model of lens pathology. The average variability in the lenticular autofluorescence measurements was 8.7%. The average ratio between lenticular autofluorescence of the left eye and that of the right eye was 0.99 +/- 0.13 SD. There was a strong correlation between age and mean lenticular autofluorescence in both eyes (correlation coefficient, 0.988; p < 0.001). The calculated annual increase in lenticular autofluorescence was 23.7 ngEq/ml. This method of measurement is reliable, and lenticular autofluorescence in tree shrews varies little among animals other than a variation caused by aging. Moreover, the tree shrew, which is believed to be a primate, is small and easy to breed. This could be a useful animal model to study various lens pathologies in humans.

Aging↗

[Fluorophotometry of the animal eye].

We assessed the usefulness of the Fluorotron Master fitted with a small animal adapter. We also discuss the measurement conditions for the tupai, which is a promising experimental mammal. A good concentration for measurements with this instrument ranged from 0.5 x 10(-6) to 1.0 x 10(-6) g/ml. A suitable time for fluorophotometry of the tupai was 30 min. after injection of fluorescein-Na, and a suitable dose of the fluorescein-Na was 2 mg/kg. We could do ultrafiltration for measurement of the protein unbound fluorescein concentration from a minimal sample of the blood using a hematocrit tube, and thus could reduce the deleterious effects of blood sampling on the animal. This instrument is useful for the estimation of the blood-ocular barrier permeability of animal models.

Animals↗

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

Aged↗

[Changes of coronary artery diameter during follow-up in patients with vasospastic angina: comparison of spastic and non-spastic sites].

The relationship between coronary vasospasticity and the development of atherosclerotic lesion was studied in 24 patients with vasospastic angina. All patients had no organic stenosis initially and underwent follow-up coronary angiography at 66 +/- 9 months after the initial examination. The coronary artery diameter was measured with the contour detection method. The spastic and non-spastic sites were identified at the initial coronary angiography with the acetylcholine provocation test. The change of the luminal diameter (delta LD) and the ratio of the change of luminal diameter (% delta LD) were compared at the spastic and the non-spastic sites. The follow-up examination showed significant decreases of coronary artery diameter in both the spastic (2.35 +/- 0.67 vs 2.16 +/- 0.58 mm, p < 0.001) and non-spastic sites (2.66 +/- 0.91 vs 2.54 +/- 0.84 mm, p = 0.02). However, delta LD and % delta LD were not different between the spastic and non-spastic sites (delta LD: -0.19 +/- 0.40 vs -0.12 +/- 0.46 mm, NS; % delta LD: -6.7 +/- 14.8% vs -3.2 +/- 17.0%, NS). In conclusion, coronary vasospasticity does not promote the development of atherosclerotic lesion.

Aged↗

Fluorophotometry with a small animal adapter.

The usefulness of the Fluorotron Master fluorophotometer fitted with a small animal adapter was evaluated with tree shrews. We also determined that the optimal measurement parameters for these animals, which are regarded as promising for experimental use in ophthalmic research, are: fluorescein-Na concentration, 0.5 x 10(-9) to 1.0 x 10(-6) g/mL; fluorescein-Na dosage, 2 mg/kg; measurement time, 30 minutes after injection of fluorescein-Na into the ocular compartments. Results indicated that ultrafiltration for the measurement of protein-unbound fluorescein can be done with a hematocrit tube and a minimal blood sample, thereby reducing the impact of the sampling on the animal's general condition. The Fluorotron Master with the small animal adapter can offer advantages in estimating the blood-ocular barrier permeability using disease models in tree shrews.

Animals↗

Cholinesterase inhibitors increase secretion of APPs in rat brain cortex.

We examined whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat. Three ChEI, both reversible and irreversible, were tested for their ability to enhance the release of nonamyloidogenic soluble derivatives (APPs). These included: physostigmine (PHY), heptyl-physostigmine (HEP) and 2,2-dichloro-vinyldimethyl phosphate (DDVP), at concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with bethanechol (BETHA). Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing.

Amyloid beta-Protein Precursor↗

NMDA receptor heterogeneity in mammalian tissues: focus on two agonists, (2S,3R,4S) cyclopropylglutamate and the sulfate ester of 4-hydroxy-(S)-pipecolic acid.

Several potent and selective agonists of the glutamate (L-GLU) receptors of N-methyl-D-aspartate (NMDA) type have been tested on the L-[3H]GLU binding to rat cortical membranes, on the depolarization of mouse cortical wedges and on the contraction of guinea pig longitudinal muscle myenteric plexus preparations with the aim of comparing the NMDA receptors present in the cortex and those present in the gut. When the depolarization of the cortical wedges was evaluated, the EC50 values of the agonists were (microM): (R,S)-(tetrazol-5-yl)-glycine (TG) 0.3; trans-4-hydroxy-(S)-pipecolic acid-4-sulfate (t-HPIS) 0.7; 1-aminocyclobutane-cis-1,3-dicarboxylic acid (ACBD) 0.8; NMDA 8; (2S,3R,4S) cyclopropylglutamate (L-CGA C) 12; quinolinic acid (QUIN) 400. When the contraction of the longitudinal muscle myenteric plexus was evaluated, the EC50 values were (microM): L-CGA C 1; TG 8; ACBD 50; t-HPIS 100; QUIN 500 and NMDA 680. When the displacement of NMDA specific L-[3H]GLU binding from rat cortical membranes was evaluated, the IC50 values were (microM): L-CGA C 0.003; TG 0.005; ACBD 0.044; t-HPIS 0.062; NMDA 0.31 and QUIN 15. No significant correlation was found when the EC50 values obtained in the ileum were plotted against the EC50 values obtained in the cortex (r = 0.47). In particular it was noted that L-CGA C was approximately three orders of magnitude more potent than NMDA when tested in the ileum but had a potency not significantly different from that of NMDA when tested in the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Dicarboxylic↗

Metrifonate effects on acetylcholine and biogenic amines in rat cortex.

The effect of systemic and local administration of metrifonate (MTF), a long-acting cholinesterase inhibitor (ChEl) on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) was investigated in the rat cortex by using transcortical microdialysis. Metrifonate (20, 40, and 80 mg/kg, s.c.) increased ACh levels in a dose-dependent manner above the baseline. Two consecutive administrations (80 mg/kg) enhanced ACh levels producing two similar patterns of elevation. A significant increase in NE was also seen at 80 mg/kg. Systemic administration (20 mg/kg) of MTF produced a significant increase of DA levels. Local cortical perfusion of MTF through the probe caused a significant but slow increase of ACh as well as an increase of NE levels. Compared to NE, the elevation of DA was more rapid and more long-lasting. The cortical levels of 5-HT were not modified by MTF given by either route. These results support the concept of MTF being a potential drug for treatment of Alzheimer disease (AD).

Acetylcholine↗

[Mitral valve prolapse: the clinical and echocardiographic characteristics in a hospital outpatient population].

BACKGROUND: Mitral valve prolapse (MVP) is generally regarded as a benign condition, but serious complications (including severe mitral insufficiency, cerebral ischemia, infective endocarditis, complex arrhythmias and sudden death) have been described in a minority of patients and have been correlated to demographic, clinical and echocardiographic characteristics. Both a lack of standardized definition of MVP in earlier studies and the different ways of recruitment of MVP patients may explain the variability in reported complication rates. METHODS: As an offspring of a larger prospective study this paper focuses on the profile of patients who were found to have MVP by M-Mode and two-dimensional echocardiography in several outpatient hospital departments. A total of 8252 consecutive subjects, examined since March 1990 to February 1991 in the Echo laboratories of the Florence area are considered; according to the presence or absence of structural changes (anterior mitral leaflet thickness > 5 mm, leaflet redundancy and/or anulus dilatation) two groups of patients with MVP (A and B) were identified. RESULTS: A MVP was diagnosed in 288 subjects (3.5%), 170 females (59%) and 118 males (41%), mean age 41 +/- 18 years (range 7-84). 110 (38%) were in Group A, 178 (62%) in Group B. The following parameters differed significantly in the two groups: age (45 +/- 17 vs 39 +/- 17 years; p < 0.003); male gender (50% vs 35%; p < 0.01); auscultatory findings (midsystolic click: 31% vs 68%; p < 0.00001; holosystolic murmur: 22% vs 3%; p < 0.00001); left ventricular diameter (53 +/- 7 vs 48 +/- 5 mm; p < 0.00001) and left atrial diameter (38 +/- 8 vs 33 +/- 5 mm; p < 0.00001). Among patients with mitral regurgitation detected by Color Doppler Echocardiography 65% were in Group A (p < 0.00001). CONCLUSIONS: These patients with MVP are obviously selected by the modality of recruitment; hence there is a higher prevalence of subjects with morphologic abnormalities and mitral regurgitation who are older and more likely to be male if compared to individuals with MVP who are found in the general population. A long-term follow-up of these patients is ongoing: owing to the data of the literature about prognostic predictors, a higher incidence of complications with a different prognosis between the two groups (with or without structural changes of the mitral valve) is expected.

Adult↗

Acetylcholinesterase protection and the anti-diisopropylfluorophosphate efficacy of E2020.

The reversible noncovalent inhibitor of acetylcholinesterase (R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methylpiperidine hydrochloride (E2020) was shown to inhibit electric eel acetylcholinesterase with high affinity in a mixed competitive-non-competitive way (Ki = 8.2 nM; Ki' = 13 nM). The pretreatment of electric eel acetylcholinesterase with E2020 dose-dependently prevented the inactivation of the enzyme by 40 microM diisopropylfluorophosphate. The EC50 for this protective effect (95% confidence limits) was 85 (76-96) nM, whereas under the same conditions E2020 IC50 was 12.3 (9.6-16) nM. E2020 injected together with atropine sulfate (17.4 mg/kg) into mice at doses in the range of 1.04-6.24 mg/kg 15 min before diisopropylfluorophosphate, caused a dose-dependent increase in diisopropylfluorophosphate LD50, resulting in protection ratios varying from 3.1 to 9.2. The effectiveness of E2020 antidotal effect was inversely correlated to the time between pretreatment and diisopropylfluorophosphate administration, being maximal when E2020 was injected 15 min, and possibly less than 15 min, before poisoning. From these experiments it is concluded that E2020 exerts a protective action against acute diisopropylfluorophosphate-poisoning in the mouse, presumably by protecting acetylcholinesterase from irreversible inactivation by this agent.

Acetylcholinesterase↗

Arrhythmias in mitral valve prolapse: relation to anterior mitral leaflet thickening, clinical variables, and color Doppler echocardiographic parameters.

Atrial and ventricular arrhythmias have been reported with variable incidence in symptomatic patients with mitral valve prolapse (MVP). The role of clinical and echocardiographic parameters as predictors for arrhythmias still needs to be clarified. One hundred nineteen consecutive patients (56 women and 63 men, mean age 40 +/- 17 years) with echocardiographically diagnosed MVP were examined. A complete echocardiographic study (M-mode, two-dimensional, and Doppler) and 24-hour electrocardiographic monitoring were performed in all patients. Complex atrial arrhythmias (CAAs) included atrial couplets, atrial tachycardia, and paroxysmal or sustained atrial flutter or fibrillation. Complex ventricular arrhythmias (CVAs) included multiform ventricular premature contractions (VPCs), VPC couplets, and runs of three or more sequential VPCs (salvos of ventricular tachycardia). The relation between complex arrhythmias and clinical parameters (age and gender) and echocardiographic parameters (left atrial and left ventricular dimensions, anterior mitral leaflet thickness [AMLT], and presence and severity of mitral regurgitation) was evaluated by multiple logistic regression analysis. CAA were present in 14% of patients and CVA in 30%. According to multiple logistic modeling, CAA correlated separately in the univariate analysis with age, presence of MR, and left ventricular and left atrial diameters; age was the only independent predictor (p < 0.001). CVA, in the univariate analysis, correlated with age, female gender, left ventricular end-diastolic diameter, and AMLT; only female gender and AMLT were independent predictors in the multivariate analysis (p < 0.01). The incidence of mitral regurgitation (59%) was higher than expected in a general population of MVP patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗