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Background Unlike age, frailty is often not taken into account in treatment indications of Endovascular treatment (EVT). One of the reason is that there was little known the relationship between frailty and the outcome of EVT for super elderly patients with peripheral artery disease (PAD). We investigate impacts of frailty on the super elderly patient prognosis who underwent EVT. Purpose To investigate impacts of frailty on the super elderly patient prognosis who underwent EVT. Methods From August 2015 to July 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we selected and analyzed 91 super elderly PAD patients (≥80 years-old) and divided them into two groups:those with moderate or higher frailty (Clinical Frailty Scale (CFS) ≥6, n=28) and those without (CFS ≤5, n=63). The primary endpoints were cardiovascular death and major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation and revascularization. Results The median follow-up period was 2.7 years. Freedom rate from cardiovascular death and MACLE were significantly lower among patients with moderate or higher frailty than among those without (47.0% vs. 58.0%, P=0.03; 39.1% vs. 68.5%, P Conclusion The prognosis of super elderly patients with moderate or higher frailty is worse than those without. Funding Acknowledgement Type of funding source: None

Reactive acid–alkali tracers have been deployed to capture the macromixing and partial segregation behaviour in an unbaffled stirred vessel. This configuration is often used in precipitators to avoid inadvertent solid accretions on vessel internals. The macromixing behaviour for semi-batch addition with visualisation of reactive (acid–alkali) tracers has been acquired via video images which are rendered visible using phenolphthalein as indicator. By means of visual reality modelling, in which computer graphics are used to reconstruct and closely mimic the experimentally visualised fluid mixing “scenes”, the parameters for a networks-of-zones mixing model for the unbaffled semi-batch case have been established. The model can then be used for predicting precipitation behaviour for single-jet and other modes of operation. Some illustrative examples for barium sulphate, showing the underlying supersaturation fields in 3-D and the consequent time evolving particle size distributions, are presented and discussed for a single jet case.

Extensive new tomographic results are reported for barium sulphate precipitation in a stirred vessel under semi-batch operation exhibiting imperfect fluid mixing. An ITS System-2000 was utilized and a linear-back-projection algorithm employed for the creation of 3-D process images. It can be concluded that electrical resistance tomography (ERT) successfully captured the sequential electrical conductivity field behaviour with both sufficient spatial and temporal resolution. It also visualized the changes in the electrical conductivity field within the vessel when changing reactant feed locations. In addition, the mixing effects on the final crystal size distributions (CSD) were also experimentally investigated. Furthermore, it is confirmed that the data obtained by ERT is effective to validate a detailed precipitation process model. A new precipitation model has been developed and combined and hybridized with a networks-of-zones model which can represent imperfect mixing in a stirred vessel. The multi-zone mixing model with order 10 3 zones is commensurate with the vessel sub-division used for tomographic imaging. The images predicted by the 3-D hybridized model are compared with the tomographic measured results, including both temporal and spatial distributions, and they show good agreement.

Precipitation in stirred vessels is a complex process involving interactions of physico-chemical nucleation and particle growth with fluid mixing. The simulation of precipitation via full CFD analysis still presents challenging computational difficulties. This paper seeks to examine how the fluid mixing influences the crystal size distribution (CSD) by applying simplified fluid mixing models. These can quantify how the separate effects of overall fluid convection, degrees of fluid macro-mixing and the extent of feed-separation determine the CSD. A new approach for describing particle growth has been developed. This model can solve the dynamic population balance equations by integration of ordinary differential equations. The model ensures the number balance as well as a mass balance on the solid, using a free discretised length grid approach. Then, the simulation under both a set of representative fluid mixing cases which varies the extent of macro-mixing (by sets of compartments or zones) and the different degrees of feed-separation (by different addition modes of the two reagents) were performed. It is predicted that joint feeds will give a larger and wider CSD, on the other hand, the most ‘extremely’ separated feeding positions can compensate for the weakness of the macro-mixing. From this practioners will be able to choose the balance of stirring intensity and feed policies to increase or reduce crystal size, as well as adjust the shape of the CSD itself for double-jet operation.

Atechnique using the visualization of reactive tracer mixing in 3-D is proposed for the quantification of mixing with chemical reaction in typical batch stirred vessel reactors. Images can be conveniently and inexpensively acquired using acid–alkali pulse tracer tests with suitable indicators. A demonstration is reported for the caustic soda– hydrochloric acid–phenolphthalein system, which produces dilute brine solution for safe disposal, on a 2.3 m3 plant-scale stirred vessel. The fluid mixing and fast acid–alkali reaction have been modelled using simplified computational fluid dynamics (CFD) based on the network- of-zones model for O(105) zones. The model predictions have been image reconstructed using AVS graphics. Using flow and mixing parameters independently acquired from inert tracer mixing tests, the close correspondence between experimental and theoretical images confirms that the micromixing must be close to perfect. The approach adopted quantifies both the local zone macromixing and macro-segregation effects for reactions faster than the fluid mixing rates and is useful for analysis of the shape and size of reagent-rich regions in semi-batch operation. Electrical resistance tomography (ERT) can suitably image the tracer mixing with reaction in 3-D according to the accompanying conductivity changes.

Objective and Design: We examined the effect of Y-24180, a potent platelet-activating factor (PAF) antagonist, on IgE-mediated cutaneous reactions in mice.¶Materials: Female BALB/c mice were used.¶Treatment: Drugs were orally administered 1 h before a dinitrofluorobenzene (DNFB) challenge or 1 h before and 12 h after the challenge.¶Methods: Biphasic increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the DNFB challenge, were induced in mice which had been passively sensitized with monoclonal anti-dinitrophenyl IgE antibody 24 h before the DNFB challenge. Ear thickness was measured with a dial thickness gauge.¶Results: Y-24180, WEB2086, ketotifen, and suplatast suppressed the IPR. Y-24180 also suppressed the LPR when administered once at 10 mg/kg or twice at 1 to 10 mg/kg. WEB2086 suppressed the LPR only when administered twice. However, ketotifen and suplatast did not suppress the LPR even when administered twice. Single administration of prednisolone significantly suppressed both the IPR and LPR.¶Conclusions: These results indicate that PAF may be involved in the induction of biphasic cutaneous reactions mediated by IgE, and Y-24180 is more effective compared with WEB2086 in this model. It is possible that the difference in the effectiveness between Y-24180 and WEB2086 depends on the persistence of those activities.

Objective and Design: Effects of Y-24180 on antigen-induced asthmatic responses were evaluated in actively sensitized guinea pigs and the effects were compared with those of several anti-asthmatic drugs.¶Materials: Male Hartley guinea pigs were used.¶Treatment: Guinea pigs were actively sensitized with ovalbumin and were pretreated with pyrilamine. Y-24180 was orally administered to the animals 3 h and others were 1 h before the antigen challenge.¶Methods: The airway hyperresponsiveness was measured according to the method of Konzett and Rossler with some modifications. The immediate asthmatic response (IAR) and late asthmatic response (LAR) were measured by the oscillation method. Inflammatory cells infiltrated into the lungs were counted after the bronchoalveolar lavage.¶Results: Under oral administration before or after the challenge with antigen, Y-24180, OKY-046, and ONO-1078 suppressed the antigen-induced airway hyperresonsiveness. Moreover, Y-24180, ONO-1078, AA-2414, and theophylline suppressed both the IAR and LAR, but OKY-046 only suppressed the LAR. Among the test drugs, only Y-24180 and theophylline suppressed the antigen-induced accumulation of eosinophils in the bronchoalveolar lavage fluid.¶Conclusions: The data indicate practical participation of PAF in the development of antigen-induced asthmatic responses in animals, and usefulness of Y-24180 in the clinical treatment of asthma as well as other anti-asthmatic drugs.

We studied the effects of (+/-)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethy l-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180), a long-acting antagonist for platelet-activating factor (PAF), on antigen-induced eosinophil infiltration and interleukin-5 (IL-5) release in the bronchoalveolar lavage fluid (BALF) of mice. Mice actively sensitized with ovalbumin (OA) were challenged by injecting intratracheally OA 3 times every fourth day. Both the number of eosinophils and level of IL-5 were significantly increased in the BALF 24 hr after the last OA challenge. Either Y-24180 or prednisolone was orally administered once a day for 10 days beginning one day before the first OA challenge. WEB2086, another PAF antagonist, was orally administered once or twice a day for 10 days. Y-24180 (0.3 - 3 mg/kg) suppressed the eosinophil infiltration in a dose-dependent manner and suppressed the IL-5 release at the highest dosage. Prednisolone (10 mg/kg) significantly suppressed both the eosinophil infiltration and IL-5 release. In contrast, WEB2086 affected neither the eosinophil infiltration nor IL-5 release when administered once a day (10 - 100 mg/kg/day). This drug never affected the IL-5 release but significantly suppressed eosinophil infiltration even when administered twice a day (30 - 200 mg/kg/day). These results indicate that the suppressive effect of Y-24180 on allergic pulmonary eosinophilia is due to not only to its long-lasting PAF-antagonism but also due to its suppressive effect on IL-5 release.

Summary A series of 4-(2-chlorophenyl)-9-methyl-6 H -thieno[3,2- f ][1,2,4]triazolo[4,3- a ][1,4]diazepine derivatives bearing substituents at the 2- and 6-positions were synthesized, and evaluated in vitro for their inhibitory activity on rabbit platelet aggregation induced by platelet activating factor (PAF) and in vivo for their preventing effect on PAF-induced mortality in mice. The length of alkyl or arylalkyl side chain at the 2-position was responsible for enhancing the affinity for the PAF receptor. The simultaneous substitution at both the 2- and 6-positions resulted in a successful separation of the affinity for the PAF receptor from that for the benzodiazepine (BZ) receptor. Thus, (±)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6 H -thieno[3,2- f ][1,2,4] triazolo[4,3- a ][1,4]diazepine (Y-24180) was confirmed to be a specific antagonist for the PAF receptor and is currently under clinical trials.

We have reported the antiulcer activities of a new compound that we named NIK-228 (3-hydroxy-methyl-2-methylimidazo [2, 1-b] benzothiazole). In the present report, we studied the antisecretory effects of NIK-228 on basal and stimulated gastric acid secretion using the Congo red sprayed method. Male Wistar rats (200 to 250 g) were used after 24 hr of fasting (without water). NIK-228, atropine and cimetidine were administered orally or intravenously 1 hr before operation for Congo red spraying. NIK-228 (100 mg/kg, p.o.), atropine (5 mg/kg p.o.) and cimetidine (100 mg/kg, p.o.) all inhibited basal gastric acid secretion. Oral administration of NIK-228 and atropine inhibited gastrin, 2-deoxy-D-glucose (2-DG) and bethanechol-induced acid secretion, but didn't inhibit histamine-induced acid secretion. Cimetidine inhibited all of histamine, gastrin, 2-DG and bethanechol-induced acid secretion. In vagotomized rats, oral and intravenous administration of atropine both inhibited bethanechol-induced acid secretion, but NIK-228 was not inhibited. These results suggested that antisecretory effects of NIK-228 were caused by the central vagal systems.

Activation of inflammatory cells by extracellular stimuli such as cytokines, viruses, allergens or oxidants lead to stimulation of intracellular amplifying signalling pathways. These activation pathways lead to enhanced inflammatory gene expression through activation of transcription factors such as nuclear factor kappa B (NF-kappa B). Upon activation, NF-kappa B translocates to the nucleus where it binds specific sites in the promoter regions of responsive genes in a time-dependent manner. This leads to the alterations in the structure of the surrounding DNA/chromatin complex resulting in local unwinding of DNA. Changes in chromatin structure occur as a result of recruitment of large, essentially pre-formed, complexes that contain chromatin remodelling factors and histone acetyltransferases (HATs) such as CREB binding protein (CBP). Acetylations of histones are regulated by HATs whose activity is controlled by a number of factors including phosphorylation. Phosphorylation of HATs by signalling pathways, differentiate themselves from those controlling specific transcription factor activation and result in enhanced transcriptional activity as a result of cross-talk between signalling pathways at the level of chromatin modifications.

Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collapsin response mediator protein)-2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture.We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal distributions. The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins. In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells.The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung.

Rapid mobilization and discharge following rapid acute phase reperfusion are recommended for elderly patients with acute myocardial infarction to achieve a better outcome and performance. The safety and efficacy of new and old treatment protocols were retrospectively compared for patients with acute myocardial infarction.The new protocol used transradial intervention, encouraged stent implantation, beta-blocker administration, and rapid mobilization for rapid discharge (10-14 day hospital stay). The previous protocol used transfemoral intervention, bed rest and late mobilization, and discouraged stent implantation and beta-blocker supplementation. High risk patients with cardiogenic shock, left main disease, malignant arrhythmia and impending myocardial rupture were excluded from the study.Thirty-two patients were treated by the new protocol, and 57 patients by the old protocol. The former included more elderly patients (p0.05). The prevalence of beta-blocker use (63.3% vs 18.8%, p0.001) and stent implantation (43.8% vs 3.5%, p0.05) were higher in the new protocol group. Hospital stay (23.6 +/- 9.5 vs 13.3 +/- 5.9 days, p0.001) and intensive care unit stay (4.4 +/- 3.0 vs 2.4 +/- 1.2 days, p0.001) were shorter in the new protocol than in the old protocol group. Rates of in-hospital death, cardiac events, systemic complications and left ventricular function (left ventricular ejection fraction and left ventricular end-diastolic volume index at admission and discharge) were not significantly different between the 2 groups. The prevalence of systemic complications (including delirium) among patients older than 70 years was lower in the new protocol group (4.7% vs 11.7%, p0.05).The new protocol can shorten hospital stay with no increase in in-hospital death or cardiac events, or decline of left ventricular function. Moreover, the new protocol is potentially effective for reducing systemic complications among elderly patients. Therefore, this protocol can be recommended for elderly patients with acute myocardial infarction.

The number of elderly patients with acute myocardial infarction has been increasing. However, the choice of treatment remains controversial. Medical records of 310 consecutive patients with acute myocardial infarction were reviewed. Two retrospective analyses were performed. 1) Patients were divided into the elderly group(70 years or more) and the younger group(under 70 years). In-hospital course and outcome were compared. 2) Pre-hospital performance status and living status were reviewed in the elderly group. Acute phase reperfusion therapy was performed in fewer patients in the elderly group(60.8% vs 71.9%, p0.01). The difference was most pronounced in cases of direct coronary angioplasty(28.6% vs 54.7%, p0.05). As a result, the rate of reperfusion success(74.8% vs 86.8%, p0.01) was lower in the elderly group. Moreover, the rates of in-hospital death(23.6% vs 6.8%, p0.005), pulmonary edema(20.3% vs 10.8%, p0.05), cardiogenic shock(11.9% vs 6.0%, p0.005), pneumonia(17.3% vs 3.0%, p0.005), and delirium(29.4% vs 12.0%, p0.001) were higher in the elderly group. Five patients in the elderly group and 3 patients in the younger group required rehabilitation because of worsened performance status. Six of them were non-reperfused patients. Elderly patients considered likely to become bed-ridden because of pre-existing physical disability at admission accounted for 28.9% of the total. Moreover, many elderly patients had poor support systems (8.4% were living alone, 21.0% were living only with their spouse or a child, 30.1% were widows or widowers). These results show that a lower acute phase reperfusion rate(especially angioplasty) resulted in a poor prognosis and worse performance status in elderly patients. Also 30% of patients were not good candidates for conventional treatment because of delirium, and that self-help in daily life is a fundamental goal for most elderly patients. Rapid and simple acute phase reperfusion, subsequent immediate mobilization, and early discharge are recommended for elderly patients with acute myocardial infarction.

To study anti-inflammatory effects of a novel indometacin ester, 3-(N,N-diethylamino) propyl-indometacin HCl (prodrug) and its ulcerogenicity in fats.Carrageenin (Car)-induced paw edema and ulcer index were examined.Car-induced paw edema was inhibited by 36.6% (P0.01) at 3 h and 34.6% (P0.01) at 5 h after a single i.p. injection of the prodrug 7.09 mg.kg-1. On the same molar basis, indometacin (Ind) 5 mg.kg-1 i.p. inhibited edema by 45.6% at 3 h and 39.2% at 5 h, however, there was no statistical significant difference (P0.05) between the edema-inhibitory effect of the prodrug and that of Ind. The dose 10 micrograms/paw exhibited 64% inhibition of the swelling, the prodrug10 micrograms/paw showed no additional inhibition of swelling; the acute gastric lesion properties of the prodrug were much lower than those of Ind 6 h after p.o.The prodrug is a potent anti-inflammatory agent with lower ulcerogenicity in the stomach.

The effect of chemical deafferentation, vagotomy (VGX), and gangliosympathectomy (GSX) on the density of fibers containing calcitonin gene-related peptide (CGRP) and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation by capsaicin abolished the density of CGRP-immunoreactive (IR) fibers, not Sub.P-IR fibers. Ten days after VGX, the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reduction of CGRP-IR and Sub.P-IR fibers was seen in submucosal and muscular layers. GSX significantly reduced the density of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosal and muscular layers. Pretreatment with 6-hydroxydopamine, a neurotoxin for noradrenergic nerves, did not affect the density of CGRP-IR fibers in the gastric wall. The density of Sub.P-IR fibers in the gastric wall was not affected by GSX. These studies indicate that the CGRP-IR and Sub.P-IR fibers in the mucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and muscle layers, that a major portion of the CGRP-IR fibers in the mucosa is of both vagal and spinal origin, and that a major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, the present results support that CGRP-IR fibers, not Sub.P-IR fibers, in the rat stomach are capsaicin-sensitive.

To investigate if identical bioavailability, rapid Tmax, and Cmax of indometacin (Ind) could be achieved when Ind is administered in rats via intranasal (ina) route.The pharmacokinetics of Ind solution at a dosage of 3 mg.kg-1 was studied after i.v., ina, and po in rats using HPLC.It showed that the time to peak (Tmax) of ina Ind 3 mg.kg-1 solution was 0.08 h, approached that after i.v. route the peak concentration (Cmax) following ina was 20.0 mg.L-1, 2.4 times higher than po dosing.It demonstrated that the ina administration of Ind was superior to po in rats, and that Ind absorption through nasal mucosa was a reasonable approach at lower doses.

Optic disc swelling was measured by computerized image analysis in diabetic patients. The subjects were divided into four groups. Group 1 contained 13 eyes without diabetic retinopathy, group 2, 14 eyes with a mild stage of simple diabetic retinopathy, group 3, 14 eyes with a severe stage of simple diabetic retinopathy and group 4, 14 eyes with preproliferative diabetic retinopathy. There were statistically significant differences in the optic disc swelling between group 1 and group 4, and between group 2 and group 4 (p0.05). The optic disc swelling increased as the stage of diabetic retinopathy progressed.

The effect of Y-24180, a potent and specific PAF antagonist, on the antigen-induced late asthmatic response in guinea-pigs was investigated. We used an asthmatic guinea-pig model which had a high incidence of dual-phase reaction and high reproducibility. Y-24180 (1 mg/kg, p.o.) had a significant inhibitory effect on the late asthmatic response and eosinophil infiltration in bronchoalveolar lavage fluid. These results suggest that PAF may play, at least partially, an important role in the development of the late asthmatic response. Thus, Y-24180 may be useful for the treatment of asthma.

We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin- or pylorus ligation (Shay)-induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine (0.03 to 3 mg/kg). Ethanol- and 0.6 N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities.

Effect of Y-20811 on airway hyperresponsiveness was studied in sensitized guinea pigs. Airway hyperresponsiveness to acetylcholine (ACh) reached maximum 7 h after antigen challenge in guinea pigs sensitized actively. Y-20811 (0.3-3 mg/kg) administered orally 3 h prior to challenge inhibited this airway hyperresponsiveness in a dose-dependent manner. Y-20811 (3 mg/kg) administered orally 4 h after antigen challenge also decreased the airway hyperresponsiveness. On the other hand, Y-20811 did not affect the bronchoconstriction induced by ACh, serotonin and histamine in nonsensitized guinea pigs. The number of eosinophils in bronchoalveolar lavage fluid in the guinea pig reached the peak 7 h after antigen challenge. Y-20811 had a tendency to decrease the number of total cells, macrophages and eosinophils in a dose-dependent manner. These results suggest that Y-20811 suppress the asthmatic mechanism which causes antigen-induced airway hyperresponsiveness.

Restless leg syndrome (RLS)を呈した梅毒性髄膜炎の1例を報告した.症例は49才男性.糖尿病,慢性活動性肝炎の加療中両下腿深部の痛くぴりぴりするような異常感覚が出現.安静で増悪,運動で軽快するため患者は夜間も歩き回り不眠であった.他覚的には神経学的異常所見を欠きRLSと診断した.血清梅毒反応陽性(STS128倍, TPHA40960倍以上),髄液細胞数増加,総蛋白増加,髄液梅毒反応陽性(STS2倍, TPHA640倍)から梅毒性髄膜炎と診断.ぺニシリンG1200万単位14日間の点滴静注で髄液所見の改善とともにRLSは急速に消失した.本例のRLSの原因に梅毒性髄膜炎による脊髄後根刺激の関与が推定され, RLSの発症機序を知るうえで重要と思われた.

Changes of gastric movements and ulcerogenic mechanisms in reserpine (6 mg/kg s.c.)-induced ulcer were studied in Wistar male rats weighing 180 to 220 g after fasting for about 20 hr. Under anesthesia with Nembutal (30 mg/kg i.p.), rats were fixed on their backs. The abdomen was incised and the stomach was exposed. Gastric movements of the fundic glandular area of greater curvature (A), the fundic-antral area of lesser curvature (B), and the neighboring area of pylorus (C) were recorded electromyographically after placing a small bipolar electrode of 1 mm distance on each area. Spontaneously, many higher amplitudes were found in area B and less found in area A. In area C, there were the least number of spikes and the lowest amplitudes. These gastric movements were inhibited until 1 hr after reserpine followed by a gradual increase in spikes and higher amplitudes. This increase was long-lasting and most marked in area B. Increased gastric movements due to reserpine were completely inhibited by atropine and vagotomy, moderately inhibited by hexamethonium and diphenhydramine, and only weakly inhibited by l-phenylephrine, l-isoproterenol, phentolamine, propranolol, metiamide, and methysergide. In reserpine-induced ulcer, ischemia occurred most markedly in area A, but erosions initiated from area B as reported previously. In area B, the gastric movements were most active, and the erosions were inhibited by the drugs which suppress gastric movements. These results suggest that reserpine-induced ulcer is due not only to the ischemia in the earlier stage, but also to the long-lasting hypermotility in the later stage.

Effects of catecholamines on plasma uric acid and allantoin levels were studied in oxonate-treated rats and non-treated rats. 1) In non-treated rats, epinephrine, isoproterenol and phenylephrine, which were injected intravenously, clearly increased plasma uric acid and allantoin, and norepinephrine had only a slight effect. The orders of potency to increase plasma uric acid and allantoin were epinephrine greater than isoproterenol greater than phenylephrine greater than norepinephrine. Beta-adrenoceptor agonists also increased plasma uric acid and allantoin in non-treated rats. The order of potency to increase plasma uric acid was isoproterenol salbutamol trimetoquinol greater than terbutaline, and that of potency to increase plasma allantoin was isoproterenol salbutamol greater than or equal to trimetoquinol greater than terbutaline. 2) In oxonate-treated rats, the four beta-adrenoceptor agonists (50 micrograms/kg, i.v.) markedly potentiated the hyperuricemic effect of oxonate. These effects of beta-adrenoceptor agonists were inhibited by propranolol (2.0 mg/kg. i.v.). In addition, the effect of isoproterenol was inhibited by butoxamine (1.0 mg/kg, i.v.), but not by atenolol (1.0 mg/kg, i.v.). These results suggest that hyperuricemia induced by catecholamines is closely related to beta 2-adrenoceptor action.

Two autopsied cases of massive unilateral cerebral infarction due to occlusion of the middle cerebral artery (MCA) were reported with special reference to presence of the secondary degeneration of the substantia nigra. Case 1 was a 70-year-old male who suddenly suffered from left hemiplegia 3 years and 2 months prior to death. CT scan showed massive infarction involving basal ganglia and fronto-parietal white matter on the right side. Some parkinsonian features such as oily face and rigidity of limbs were noted during the course. At autopsy, the proximal portion of rt MCA was found occluded and the right substantia nigra was found depigmented. Case 2 was a 71 year-old male who suddenly became hemiplegic 4 years prior to death. CT scan revealed a low density area in the corona radiata of the right cerebral hemisphere. On carotid antiography, complete obstruction of the horizontal portion of right MCA at its distal end was observed, which was confirmed at autopsy. Histologically, the right substant a nigra in case 1 showed marked neuronal loss with gliosis as well as presence of many extracellular melanin pigments. These changes were more prominent in its medial portion where chromatolytic neurons were occasionally seen. The adjacent fronto-pontine tract and pyramidal tract showed secondary degeneration. The left substantia nigra appeared normal. In case 2, the substantia nigra on both sides appeared normal. The whole right cerebral peduncle, on the other hand, showed diffuse myelin pallor.(ABSTRACT TRUNCATED AT 250 WORDS)

Two patients with herpes simplex encephalitis were studied with N-Isopropyl I-123 p-Iodoamphetamine (IMP) single photon emission computed tomography (IMP-SPECT) and X-ray computed tomography (CT). In both cases the affected temporal lobes showed an increased IMP uptake. In case 1, the initial increased IMP uptake decreased as symptoms and CT findings improved. In case 2, the increased IMP uptake was shown at the time of symptoms progressed, while CT had no abnormal findings. IMP uptake is sensitive for its demonstration of inflammatory processes of herpes simplex encephalitis.

Corticosteroids are by far the most effective treatment for chronic inflammatory diseases such as asthma. Inflammation in asthma is characterized by the increased expression of multiple inflammatory genes, including those that encode cytokines, chemokines, adhesion molecules, and inflammatory enzymes and receptors. Increased expression of inflammatory genes is regulated by pro-inflammatory transcription factors, such as nuclear factor κB (NF-κB). These bind to, and activate, co-activator molecules that then acetylate core histones resulting in elevated gene transcription. Corticosteroids reverse histone acetylation at the site of inflammatory gene transcription, either by direct binding of the activated glucocorticoid receptor to NF-κB-associated co-activators or by recruitment of histone deacetylases to the activated transcription complex. Understanding how corticosteroids work in asthma may help in designing novel corticosteroids with fewer systemic effects, as well as novel anti-inflammatory approaches.