Coronary endothelium-protective effects of defibrotide in ischaemia and reperfusion

Summary Defibrotide is known to enhance prostacyclin (PGI₂) release from the vascular endothelium. We investigated the vasoactive effects of defibrotide in isolated rat hearts perfused at constant flow subjected to ischaemia and reperfusion. Defibrotide at 10^–7 or 100 g/ml did not exert any direct vasoactive effect on normal rats hearts. However, ischaemia and reperfusion resulted in an impaired vasodilation to acetylcholine, an endothelium-dependent vasodilator. In contrast, the vasodilator response to the endothelium-independent dilator, nitroglycerin, was unaffected. Defibrotide, at 10^–7 or 100 g/ml, markedly restored the vasodilation to acetylcholine 10^–7 nmol/l to 1 mol/l (P < 0.01) without influencing the vasodilator response to nitroglycerin (2 to 200 g/1). Haemoglobin (150 nmol/l) inhibited the dilation to acetylcholine in response to defibrotide. However, no evidence of (PGI₂) release was observed with acetylcholine-induced vasodilation in the presence or absence of defibrotide. Additionally, 10–100 g/ml of defibrotide did not significantly decrease superoxide radicals generated by a xanthine-xanthine oxidase synthetic system under conditions in which superoxide dismutase was effective. Thus, defibrotide appears to exert an endothelium-protective effect preserving endothelium-derived relaxing factor (EDRF) without directly scavenging free signals.Supported in part by Research Grant No. HL-25575 from the National Heart, Lung and Blood Institute of the NIH Send offprint requests to A. M. Lefer at the above address     

Gerstmann-Sträussler-Scheinker disease showing β-protein type cerebellar and cerebral amyloid angiopathy

Cerebral amyloid angiopathy is observed in several brain degenerative disorders, but this pathological condition has received little attention in Gerstmann-Sträussler-Scheinker disease (GSS). We report a 69-year-old man who showed the cardinal features of GSS together with typical and extensive congophilic angiopathy. Immunohistochemical studies revealed that the vast majority of the amyloid plaques present in the brain of this patient were consistently labeled by anti-prion protein (PrP) antibody. Double immunostaining disclosed many additional -protein immunoreactive plaque-like lesions, including a special type of hybrid plaque with colocalization of PrP and -protein (-PrP). The vascular amyloid deposits seen in both the cerebellum and cerebrum were immunoreactive only to anti--protein antibody. It seems likely that the extensive deposition of -protein amyloid (including brain vascular amyloidosis) seen in this and other similar cases is part of pathology of GSS, although the possibility that this finding is due to ageing or concomitant Alzheimer's disease cannot be completely ruled out.Supported by a research grant from the Intractable Disease Division, Ministry of Health and Welfare, Primary Amyloidosis Research Committee, Japan     

Gamete development inPlasmodium berghei regulated by ionic exchange mechanisms

Ionic regulation in the induction of exflagellation ofPlasmodium berghei was investigated by culturing the parasites in various isotonic media. Of the salts tested, NaHCO₃ exhibited the highest activity in inducing exflagellation, whereas KHCO₃ showed no activity. In the absence of HCO ₃ ^– , media containing monovalent cation (Na⁺, K⁺, Cs⁺, Rd⁺, choline⁺, lysine⁺, arginine⁺) and Cl^– also induced exflagellation, but their activities were lower than that of NaHCO₃. Anions of Br^– or NO ₃ ^– could be substituted with Cl^–, whereas other anions such as I^–, NO ₂ ^– , SO ₄ ^2– , SCN^–, H₂PO ₄ ^– , or HPO ₄ ^2– failed to induce exflagellation, as did tetramethylammonium-Cl, CaCl₂, MgSO₄, MgCl₂ and sucrose as well. These results suggest that the induction of exflagellation requires the presence of Na⁺ and HCO ₃ ^– or monovalent, membrane-permeable cation and Cl^– in the medium. Measurements of the efflux of H[¹⁴C]O ₃ ^– or Cl^– indicated that these anions were released from the cells into the NaCl or the NaHCO₃ medium, respectively, probably by exchange in HCO ₃ ^– /Cl^–. Determination of intracellular ionic concentrations by electron microscopic X-ray microanalysis of cryopreserved specimens revealed that in the NaHCO₃ medium, external Na⁺ (and probably HCO ₃ ^– ) enters the gametocytes by exchange with internal Cl^– (and probably H⁺), whereas in Cl^–-containing media, external unspecified cation and Cl^– influx by exchange, probably with H⁺ and HCO ₃ ^– . It is therefore suggested that two separate ion exchangers, i.e., Na⁺-dependent HCO ₃ ^– (in)/Cl^–(out) and nonspecific monovalent-cation-dependent Cl^–(in)/HCO ₃ ^– (out) exchangers, are involved in the induction of gametogenesis inP. berghei. Furthermore, the presence of both classes of anion in the medium enhanced exflagellation activity and increased Na⁺ uptake more than did the NaCl or NaHCO₃ medium alone. The apparent synergistic enhancement by two contraactive anion exchangers is consistent with a recycling model of pH_i regulation, in which HCO ₃ ^– and Cl^– are exchanged between the cells and the media, resulting in the acceleration of monovalent cation/H⁺ exchange.This work was supported by a Grant-in-Aid (No. 01570212) from the Ministry of Education, Science and Culture, Japan and the Ohyama Health Foundation, Japan (to FK), and in part by the Medical Research Council, United Kingdom (to RES)     

m-Dinitrobenzene intoxication due to skin absorption

Summary A case of m-dinitrobenzene intoxication is described. Clinical picture of the patient who was exposed to an industrial material containing m-dinitrobenzene, methaemoglobinemia and excretion of urinary metabolites observed in a volunteer who experimentally worked with the same material, absence of m-dinitrobenzene in the ambient air during the exposure, and penetration of m-dinitrobenzene through the protective gloves which were used by the patient indicate that m-dinitrobenzene was the toxic agent and that the main route of the invasion was skin absorption.     

A new simply and effective fractionation method for cylindrospermopsin analyses.

A new simply and effective fractionation method for cylindrospermopsin (CYN) analyses was developed. The extract from cells of Cylindrospermopsis raciborskii was resuspended with 0.1 M carbonate buffer at pH 10.5, and pass through the double-cartridges column which was consisted of a styrene polymer cartridge and an anion exchange cartridge. CYN and deoxy-CYN were adsorbed with the anion exchange cartridge. After separation of the anion exchange cartridge, adsorbed compounds were eluted from the cartridge with 50% methanol containing 1% formic acid solution. CYN and deoxy-CYN were selectively condensed in the eluted solution. When CYN was analyzed by LC-photodiode array or LC/MS, only two peaks of CYN and deoxy-CYN were detected quantitatively. The results suggest that the fractionation method is a useful method for CYN analyses and must be utilized for CYN purification.     

Predicting outcome of one-step total hysteroscopic resection of sessile submucous myoma

STUDY OBJECTIVE: To analyze variables for successful 1-step hysteroscopic myomectomies of sessile submucous myomas. DESIGN: Retrospective case-control study. (Canadian Task Force classification II-2). SETTING: Single operator's practice in a university hospital and its related hospitals. PATIENTS: Twenty-eight patients with sessile submucous myomas and menorrhagia, infertility, or both. INTERVENTIONS: Our strategy for hysteroscopic myomectomy is as follows. First, we scraped and/or vaporized intrauterine dome of myoma until top of myoma was even with level of wall of cavity. Next, the remnant intramural node was squeezed by uterine contractions induced by prostaglandin F2alpha injection. Finally, the newly raised myoma dome was sectioned or vaporized electrosurgically only within the space of the intrauterine cavity and/or was separated mechanically from healthy myometrium without electrosurgery. MEASUREMENTS AND MAIN RESULTS: Submucous myomas in 16 (57.1%) patients were completely removed after 1 surgery. By logistic regression analysis, thickness of outer myometrial layer of myoma node (OR 3.06, p = .02), myoma size (OR 0.86, p = .04), and intramural extension degree (OR 0.91, p = .03) were significantly associated with outcome of complete resection. CONCLUSION: Thickness of outer myometrial layer of myoma node, myoma size, and intramural extension degree predicted outcome of 1-step hysteroscopic myomectomy. The chance of performing successful surgery increased with increased thickness of outer myometrial layer of myoma, and decreased with larger myomas and greater degrees of intramural extension.     

Two Lambert-Eaton Myasthenic Syndrome Patients with Ameliorated Activities of Daily Living Due to Cholinesterase Inhibitors

We herein report two P/Q-type voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS) patients who responded dramatically to cholinesterase inhibitors. Patient 1, a 76-year-old man, had small-cell lung cancer and developed LEMS during chemotherapy. When symptomatic treatment was started with pyridostigmine, gait disturbance was ameliorated, and his modified Rankin scale decreased from 4 points to 3 points. Patient 2, a 68-year-old man, had cancer-free LEMS. Distigmine bromide was very effective and ameliorated not only his gait disturbance but also autonomic symptoms, and his modified Rankin scale decreased from 2 points to 1 point. Cholinesterase inhibitors alone may be effective in a small portion of LEMS patients.     

Measures of Perceived Neighborhood Food Environments and Dietary Habits: A Systematic Review of Methods and Associations

Access to healthy food is a necessity for all people. However, there is still a lack of reviews on the assessment of respondent-based measures of neighborhood food environments (perceived food environments). The aim of this systematic review was to evaluate the measurement tools for perceived food environments by five dimensions of food access and to obtain the overview of their associations with dietary habits among people aged 18 years and older in middle- and high-income countries. Observational studies using perceived food environment measures were identified through a systematic review based on two databases for original studies published from 2010 to 2020. A total of 19 final studies were extracted from totally 2926 studies. Pertaining to the five dimensions of food access, 12 studies dealt with accessibility, 13 with availability, 6 with affordability, 10 with acceptability, 2 with accommodation, and 8 with a combination of two or more dimensions. Perceived healthy food environments were positively associated with healthy dietary habits in 17 studies, but 8 of them indicated statistically insignificant associations. In conclusion, this review found accessibility and availability to be major dimensions of perceived food environments. The relationship between healthy food environments and healthy diets is presumably positive and weak.     

Blocking L-type calcium channels enhances long-term depression induced by low-frequency stimulation at hippocampal CA1 synapses

Specific contributions of voltage-dependent calcium channels (VDCCs) to induction of long-term depression (LTD) have not been thoroughly elucidated. The present study examined roles of T- and L-type VDCCs in N-methyl-D-aspartate (NMDA) receptor-dependent LTD induced at several different levels of synaptic activation (0.5- to 10-Hz presynaptic stimulations) at Schaffer collateral-CA1 synapses in rat hippocampal slices. Blockade of T-type VDCCs with nickel ions failed to change LTD magnitude at all levels of stimulation. However, blockade of L-type VDCCs reduced LTD in response to stimulation at 1 and 2 Hz and, conversely, enhanced LTD at a lower frequency (0.5 Hz). The enhancement of 0.5-Hz LTD under L-type VDCC blockade was shown pharmacologically to depend on NMDA receptors (NMDARs) and intracellular Ca(2+) release. Calcium imaging revealed that contribution of L-type VDCC-mediated calcium influx to the total calcium increase was greater during 0.5-Hz stimulation than during 1.0-Hz stimulation. This finding, combined with the reported suppression of NMDARs mediated by L-type VDCCs, may be relevant to the present enhancement of 0.5-Hz LTD due to L-type VDCC blockade.