Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies

Guillain–Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.     

Osteocytes in chronic uremia

Summary Differential counts of osteocytes were performed in human cortical femoral bone of 40 patients with chronic renal failure and of 40 patients without skeletal disease. In undecalcified ground sections (50–70 µ) stained with basic fuchsine, osteocytes were differentiated into small (=neutral) osteocytes, enlarged (=metabolically activated) osteocytes and empty lacunae (=dead osteocytes). In uremia the fraction of activated cells and of empty lacunae is markedly increased, whereas the fraction of small neutral osteocytes is reduced. These findings are somewhat more pronounced in Haversian than in interstitial bone. The activated osteocytes are randomly distributed in Haversian systems and do not accumulate in the outer and older parts of individual osteones of uremic or nonuremic subjects. These findings are presumably caused by elevated serum parathyroid hormone levels, which lead to increased activation of osteocytes. Activation of osteocytes may induce shortening of osteocyte survival time.

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Zusammenfassung In der Corticalis der Femurdiaphyse wurden bei 40 Patienten mit chronischer Niereninsuffizienz und bei 40 skeletgesunden Kontrollpersonen Osteocyten-differentialzählungen durchgeführt. An unentkalkten Knochendünnschliffen wurde nach Färbung mit basischem Fuchsin der Anteil der kleinen neutralen Osteocyten, der großen metabolisch aktivierten Osteocyten und der Anteil der leeren Osteocytenlakunen ausgezählt. In der Corticalis steigt bei chronischer Niereninsuffizienz die Zahl der großen aktivierten Osteocyten und der leeren Lakunen signifikant auf Kosten der kleinen Osteocyten an. Die Veränderungen sind in Haversschen Osteonen etwas stärker ausgeprägt als in interstitiellen Knochenlamellen.Aktivierte Zellformen sind in den äußeren älteren Abschnitten der Osteone nicht häufiger anzutreffen als in der Nähe des Gefäßkanals. Die Befunde werden auf eine vermehrte Aktivierung der Osteocyten unter dem Einfluß erhöhter Serum-Parathormonspiegel zurückgeführt. Die Zunahme aktivierter Zellen und leerer Osteocytenlakunen deutet auf eine Verkürzung der Osteocytenlebenszeit bei sekundärem Hyperparathyreoidismus hin. Die gesteigerte metabolische Aktivität der Osteocyten in der Urämie ist angesichts der urämischen Störung des Calciumstoffwechsels mit Hypocalcämie bemerkenswert.

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With support of Deutsche Forschungsgemeinschaft. Presented in part at the 1. Workshop on Bone Morphometry, Ottawa, Canada, March 1973.     

Lithium-induced uremia in rats — a new model of chronic renal failure

Three groups of new-born rats were studied: Group Li/Li treated with Li for 16 weeks, group Li/C treated for 8 weeks followed by 8 weeks without Li, and Group C/C 16 weeks old controls. Both Li-treated groups showed severe reduction of renal function, particularly group Li/Li, where the mean GFR was reduced by 80%. Plasma urea, creatinine, and osmolality were increased, blood hemoglobin and hematocrit were reduced, whereas plasma Na, K, and standard bicarbonate were unchanged. Na clearance was maintained and fractional Na excretion thus increased. Fractional Li excretion was also increased, indicating inhibition of proximal tubular salt and water reabsorption. Renal concentrating ability was markedly reduced. When Li was withdrawn, plasma urea levels remained unchanged or continued to rise, and the concentrating defect persisted. The results demonstrate that Li administration to new-born rats causes irreversible chronic renal failure which may progress even in the absence of Li. This model of chronic renal failure has several characteristics in common with chronic renal failure in humans.     

Altered monocyte function in uremia

Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.     

Effect of acute and chronic administration of caffeine on pain-like behaviors in rats with partial sciatic nerve injury

Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic caffeine administration in rats after partial sciatic nerve injury. The hindpaw response to mechanical or cold stimulation was assessed following photochemically induced sciatic nerve injury which leads to hypersensitivity to these stimuli. Caffeine was administered i.p. acutely or in the drinking water chronically. The mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose-dependently alleviated by acute systemic administration of caffeine (10-80 mg/kg). The effect of caffeine was, however, associated with side effects including locomotor stimulation or depression. Chronic oral administration (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine starting at the time of nerve injury did not significantly affect the development of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced neuropathic pain state in nerve-injured rats, but only at very high doses. The potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have been compensated for by an antinociceptive effect of caffeine through antagonism of A2A receptors and tolerance development.     

Sympathetic nerve function and vascular reactivity in Doca-salt hypertensive rats

The present study was conducted to measure norepinephrine release during sympathetic nerve stimulation and to evaluate vascular reactivity in the isolated perfused mesenteric vasculature of normotensive and Doca-salt hypertensive rats. Significantly greater vasoconstrictor responses to periarterial nerve stimulation, norepinephrine, and vasopressin, but not to barium chloride, were observed in the mesenteric vasculature of the hypertensive rats in comparison with the control normotensive group. Norepinephrine release, measured as total tritium overflow, during periarterial nerve stimulation at 4 Hz for 2 min, was identical in both normotensive and hypertensive animals. Phentolamine (5.3 micro M) significantly increased tritium overflow, but to the same extent in the normotensive and the hypertensive mesenteric vasculature, suggesting that the negative feedback presynaptic alpha-adrenoceptor mechanism, which has been proposed to modulate transmitter release, was unaltered in this form of hypertension. These results indicate that hyperresponsiveness of the mesenteric vasculature to periarterial nerve stimulation in the hypertensive rats is due to increased sensitivity of the vascular alpha-adrenoceptor and not facilitation of the transmitter release. The increased vascular reactivity to norepinephrine and vasopressin may be involved in the maintenance of Doca-salt hypertension.     

急、慢性高原缺氧对成年大鼠空间学习和记忆功能的影响

 目的： 探讨急性和慢性高原缺氧对成年大鼠空间学习和记忆功能的影响。方法： 研究分三部分。实验一：成年雄性SD大鼠分为平原组（A组）和急性高原缺氧组（B组）（n=15）,B组于低压舱模拟海拔7 000 m高原连续暴露72 h后返回平原,24 h后两组同时进行Morris水迷宫定位巡航实验,连续训练3 d,每天4次,记录大鼠寻找平台的时间,第4天撤除平台,进行空间探索实验并记录大鼠穿越平台的次数和在目标象限停留的时间。实验二：成年雄性SD大鼠分为平原组（C组）和慢性高原缺氧组（D组）（n=13）,D组置于低压舱模拟海拔6 000 m高原连续暴露35 d后返回平原,24 h后两组同时进行Morris水迷宫定位巡航实验,连续训练5 d,每天4次,第6天进行空间探索实验。实验三：成年雄性SD大鼠先进行Morris水迷宫定位巡航实验和空间探索实验(方法同实验二）,于空间探索实验后随机分为平原组（E组）和急性高原缺氧组（F组）（n=15）,F组于低压舱模拟海拔7 000 m高原连续暴露72 h后返回平原,2 h后两组再同时进行空间探索实验。结果： B组缺氧暴露后第1天寻找平台的时间较A组显著缩短（P<0.05）,B组穿越平台次数和在目标象限停留时间百分比与A组比较差异无统计学意义。D组寻找平台潜伏期时间、穿越平台次数及在目标象限停留时间的百分比与C组相比,差异均无统计学意义。F组与E组缺氧前的各项指标均无显著差异,缺氧暴露后,F组穿越平台次数和在目标象限停留时间的百分比与E组相比差异无统计学意义。结论： 在本实验观察期内,急、慢性模拟高原缺氧对成年雄性大鼠对空间位置觉和方向觉（空间定位）的学习和记忆能力无显著影响（P>0.05）。急、慢性高原缺氧对工作记忆和空间参考记忆等功能的影响有待进一步研究。