Symptomatic compression of the optic nerve by the carotid artery: clinical profile of 18 patients with 24 affected eyes identified by magnetic resonance imaging.

OBJECTIVE: To characterize the clinical features and course of patients with magnetic resonance imaging (MRI)-defined optic nerve compression by the supraclinoid carotid artery. DESIGN: Retrospective, observational case series. PARTICIPANTS: Eighteen patients with 24 affected eyes were identified by reviewing case records from the author's referral-based neuro-ophthalmology practice. Predetermined inclusion and exclusion criteria were applied to potential participants. MAIN OUTCOME MEASURES: The following variables were abstracted from the medical record: age, gender, presenting symptoms, past medical problems, visual acuity, color vision, visual field, pupillary reactions, optic disc appearance, other neurologic signs, and previously documented and follow-up examinations. RESULTS: There were eight women and ten men ranging in age from 28 to 86 years (median age, 72 years) at the time of diagnosis. Ten (56%) of 18 patients had hypertension. Twelve patients had unilateral optic neuropathy, whereas 6 patients had bilateral optic neuropathy. One patient presented with subacute superior orbital fissure syndrome due to mass effect of a dolichoectatic carotid artery. Another patient had oculomotor nerve palsy with signs of aberrant regeneration due to intracavernous mass effect of a dolichoectatic carotid artery. One patient had a bitemporal hemianopia associated with bilateral compression of the immediate prechiasmatic optic nerves by dolichoectatic carotid arteries. The predominant pattern of visual field loss in most patients reflected nerve fiber bundle injury. A central scotoma or absolute central visual field loss was noted in only 6 (25%) of 24 affected eyes. Most patients demonstrated saucerlike excavation of the optic disc. Progression of visual acuity loss occurred at a relatively slow rate. CONCLUSIONS: Although uncommon, intracranial compression of the optic nerve by the carotid artery should be considered in a patient with unexplained or progressive unilateral or bilateral optic neuropathy. This entity can be diagnosed using clinical skills to exclude more common causes of optic nerve injury and coronal-oriented MRI to confirm anatomic compression of the symptomatic optic nerve. Although many affected patients have excavation of the optic disc and nerve fiber bundle visual field defects, most have additional signs atypical for glaucoma, minimizing the potential for diagnostic confusion between the two disorders.     

Focal segmental membranous glomerulonephropathy associated with other glomerular diseases

In four patients with the nephrotic syndrome, renal biopsy revealed focal segmental membranous glomerulonephropathy (FSMGN) associated with the histologic patterns of "nil" disease (two cases), hereditary nephritis and diffuse diabetic glomerulosclerosis. The occurrence of FSMGN in association with other glomerular diseases, presumably unrelated to immune complex deposition, is infrequent in our experience. Rather than necessarily representing an early stage or milder form of membranous glomerulonephropathy, it may be an epiphenomenon. This interpretation has prognostic and therapeutic implications and raises important pathogenetic questions. In particular, this study suggests that in some instances, preexisting functional and structural abnormalities may play a role either in the deposition of preformed circulating immune complexes or in the local formation of immune complexes.     

Vergleich veränderter Bewußtseinszustände unter den Halluzinogenen (−)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) und N,N-Dimethyltryptamin (DMT)

Zusammenfassung Die Untersuchung vergleicht unter Verwendung zweier Placebo-Kontrollgruppen veränderte Bewußtseinszustände, die unter den Halluzinogenen (–)⁹-trans-Tetrahydrocannabinol (⁹-THC) und N,N-Dimethyltryptamin (DMT) auftreten. 24 Probanden erhielten 250g ⁹-THC p.o. pro kg Körpergewicht, und 26 Probänden wurde 250g DMT pro Körpergewicht i.m. appliziert. Die Placebogruppe bestand aus insgesamt 24 Probanden. Die Effekte wurden retrospektiv mit einem Fragebogen erfaßt, dessen Items nach inhaltlichen und testtheoretischen Gesichtspunkten zu den folgenden 8 Skalen zusammengefaßt wurden: Optische Sinnestäuschungen, akustische Sinnestäuschungen, Konzentrations- und Gedächtnisstörungen, Derealisationserscheinungen, Depersonalisationserscheinungen, Leiberlebensveränderungen, euphorisches Zustandsbild und dysphorisches Zustandsbild.In allen acht Syndromen unterschieden sich die beiden Halluzinogene signifikant von Placebo. Zwischen den Halluzinogenen konnte jedoch keine signifikante Differenz nachgewiesen werden. In der Skala optische Sinnestäuschungen zeigte sich als Tendenz, daß DMT hier eine stärkere Wirkung als ⁹-THC entfaltet.Methodische Probleme des Vergleichs verschiedener Halluzinogene werden diskutiert.     

Characterizing the influence of structure and route of exposure on the disposition of dithiocarbamates using toluene-3,4-dithiol analysis of blood and urinary carbon disulfide metabolites.

Differences in the toxicities observed for dithiocarbamates have been proposed to result from the influence of nitrogen substitution, oxidation state, and route of exposure. To better characterize the fate of dithiocarbmates in vivoas a function of structure and route of exposure, rats were administered equimolar doses of carbon disulfide (CS2), N-methyldithiocarbamate, pyrrolidine dithiocarbamate, N,N-diethyldithiocarbamate, or disulfiram daily for five days, either po or ip, and sequential blood samples obtained. Protein dithiocarbamates formed by the in vivo release of CS2, parent dithiocarbamate, and protein-bound mixed disulfides were assessed in plasma and hemolysate by measuring toluene trithiocarbonate generated upon treatment with toluene-3, 4-dithiol (TdT). To aid in determining the bioavailability of CS2 from the administered dithiocarbamates, the urinary CS2 metabolites, 2-thiothiazolidine-4-carboxylic acid (TTCA) and 2-thiothiazolidin-4-ylcarbonylglycine (TTCG), were also determined. The levels of TdT-reactive moieties detected depended upon both the compound administered and the route of exposure. Parent dithiocarbamates, with the exception of disulfiram, were eliminated from blood within 24 h; but protein associated TdT-reactive moieties persisted and accumulated with repeated exposure, regardless of the route of exposure. N-Methyldithiocarbamate demonstrated the greatest potential to produce intracellular globin modifications, presumably through its unique ability to generate a methylisothiocyanate metabolite. Urinary excretion of TTCA and TTCG was more sensitive than TdT analysis for detecting dithiocarbamate exposure, but TdT analysis appeared to be a better indicator of in vivo release of CS2 by dithiocarbamates than were urinary CS2 metabolites. These data suggest that CS2 is a more important metabolite, following oral exposure, than are other routes of exposure, e.g., inhalation or dermal. In addition, data also suggest that acid stability, nitrogen substitution, and route of exposure are important factors governing the toxicity observed for a particular dithiocarbamate.     

Synthesis and physico‐chemical properties of peptides in soil humic substances

Abstract: Soil humic substances (HS) are heterologous, polydispersive, and multi‐functional organometallic macromolecules ubiquitous in soils and sediments. They are key players in the maintenance of the belowground ecosystems and in the bioavailability of both organic and inorganic contaminants. It is widely assumed that the peptidic substructures of HS are readily degraded and therefore do not contribute significantly to interactions with contaminants such as toxic metals. To investigate the turnover of humified peptides, laboratory soil aging experiments were conducted with ¹³C‐glucose or ¹⁵N‐nitrate for 8.5 months. Evidence for random‐coil peptidic structures in the labeled HS was obtained from 2‐D nuclear magnetic resonance (NMR), pyrolysis gas chromatography‐mass spectrometry (pyro‐GC‐MS), and circular dichroism data. Interaction of metals with the peptidic carbonyls of labeled HS was rationalized from the solid‐state NMR data. Detailed ¹³C and ¹⁵N labeling patterns of amino acid residues in the acid hydrolysates of HS acquired from NMR and GC‐MS revealed two pools of peptides, i.e. one extant (unlabeled) and the other, newly humified with little isotopic scrambling (fully labeled). The persistence of pre‐existing peptidic structures indicates their resistance to degradation while the presence of fully labeled peptidic amino acids suggests wholesale incorporation of newly synthesized peptides into HS. These findings are contrary to the general notion that humified peptides are readily degraded.     

抗癌作用新靶点及其抑制剂的研究进展

针对靶点分子或某种发生发展机制来设计抗肿瘤药物的研究工作已取得了相当大的成就.这类药物的特异性强,疗效显著,因此,针对这些新靶点进行药物设计可以使抗肿瘤药物的研究产生一次新的革命.本综述旨在讨论目前抗肿瘤药物研究的潜在的新靶点以及它们相应的抑制剂或拮抗剂.     

N-甲基-D-天门冬氨酸受体及其调控的钙内流在大鼠感染性脑损伤中的变化

为探讨Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体及其调控的钙内流在感染性脑损伤发病机制中的作用，采用Ｆｕｒａ－２／Ａｍ荧光法检测大鼠大脑皮质突触体内游离钙浓度（［Ｃａ＋＋］ｉ）。结果表明，注射百日咳杆菌组的［Ｃａ＋＋］ｉ较对照组显著增加（Ｐ均＜０．０１），并与注菌时间呈正相关关系（４小时ｖｓ０．５小时和２４小时ｖｓ４小时，Ｐ＜０．０５和＜０．０１）。ＮＭＤＡ受体的非竞争性拮抗剂ＭＫ－８０１预处理组（ＭＢＰ）的［Ｃａ＋＋］ｉ、脑含水量和伊文思蓝含量均较注菌组显著减少（Ｆ值分别为７２．２５、１６．８９、１４．３６，Ｐ＜０．０１和＜０．０５），并以２４小时［Ｃａ＋＋］ｉ减少最为明显（Ｐ＜０．０１）。提示ＮＭＤＡ受体调控的神经元内钙超载在感染性脑损伤、尤其在迟发性脑损伤的发病机制中起着重要作用。     

Fate and distribution of brevetoxin (PbTx) following lysis of Karenia brevis by algicidal bacteria, including analysis of open A-ring derivatives

Flavobacteriaceae (strain S03) and Cytophaga sp. (strain 41-DBG2) are algicidal bacteria active against the brevetoxin (PbTx)-producing, red tide dinoflagellate, Karenia brevis. Little is known about the fate of PbTx associated with K. brevis cells following attack by such bacteria. The fate and distribution of PbTx in K. brevis cultures exposed to these algicidal strains were thus examined by receptor binding assay and liquid chromatography/mass spectrometry (LC/MS) in three size fractions (>5, 0.22–5, <0.22 μm) over a 2-week time course. In control cultures, brevetoxin concentrations in the >5 μm particulate size fraction correlated with changes in cell density, whereas significant increases in dissolved (i.e., <0.22 μm) toxin were observed in the later stages of culture growth. Exposure of K. brevis to either of the two algicidal bacteria tested caused cell lysis, coinciding with a rapid decline in the >5 μm PbTX size fraction and a simultaneous release of dissolved toxin into the growth medium. Upon cell lysis, dissolved brevetoxin accounted for ca. 60% of total toxin and consisted of 51–82% open A-ring derivatives. Open A-ring PbTx-2 and PbTx-3 derivatives bound with lower affinity (approximately 22- and 57-fold, respectively) to voltage-gated sodium channels and were considerably less cytotoxic (86- and 142-fold, respectively) to N2A cells than their individual parent toxins (i.e., PbTx-2 and PbTx-3). These novel findings of changes in PbTx size-fractioned distribution and overall reduction in K. brevis toxicity following attack by algicidal bacteria improve our understanding of potential trophic transfer routes and the fate of PbTx during red tide events. Moreover, this information will be important to consider when evaluating the potential role of algicidal bacteria in harmful algal bloom (HAB) management strategies involving control of bloom populations.     

广藿香内生真菌撕裂耙齿菌A878次级代谢产物研究

目的 研究药用植物广藿香Pogostemon cablin内生真菌撕裂耙齿菌Irpex laceratus A878的活性次级代谢产物。方法 运用硅胶、Sephadex LH-20、HPLC等多种柱色谱技术以及重结晶方法对发酵产物进行分离纯化,并利用¹H-和¹³C-NMR、UV等谱学方法鉴定化合物结构。采用SRB法和Griess法测定化合物的生物活性。结果 从广藿香内生真菌撕裂耙齿菌A878固体发酵产物中分离鉴定了2个新化合物和10个已知化合物。分别为撕裂耙齿菌内酯A(1)、撕裂耙齿菌内酯B(2)、细胞松弛素H(3)、细胞松弛素J(4)、18-甲氧基细胞松弛素J(5)、去乙酰基细胞松弛素H(6)、细胞松弛素J₃(7)、拟茎点霉(口山)酮A(8)、狄瑟酚A(9)、桔青霉三酚A(10)、(22E,24R)-麦角甾-5,7,22-三烯-3β-醇(11)和1S,2R,4S-三羟基-对-薄荷烷(12)。结论 化合物1、2为新的吡喃内酯类化合物。活性研究表明化合物4、5和9对人神经癌SF-268细胞、人乳腺癌MCF-7细胞、人肝癌H...