Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia

The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), is activated in experimental models of chronic pain, and is also activated by oestrogen. We used an established model of inflammatory trigeminal pain, injection of Complete Freund's Adjuvant (CFA) into the masseter muscle, to determine whether ERK activation may play a role in hormone-related trigeminal pain disorders. We measured withdrawal responses to stimulation of the masseter (V3, primary allodynia) and whisker pad (V2, secondary allodynia) using graded monofilaments. Oestrogen treatment in the presence of inflammation increased withdrawal response to stimulation of both masseter and whisker pad compared with inflammation alone, indicating an additive effect of inflammation and oestrogen on both primary and secondary allodynia. We examined ERK activation in trigeminal ganglia from each treatment group using western blot and immunohistochemistry. Both masseter inflammation and oestrogen treatment increased ERK activation, and combined treatment had an additive effect. Both masseter inflammation and oestrogen increased the percentage of pERK immunoreactive neurons in divisions 1 and 2 (V1/2), and combined treatment increased pERK immunoreactivity in V1/2 compared with inflammation alone. We stereotactically administered ERK antagonist U0126, or inactive control U0124, to the trigeminal ganglion of CFA+E2-treated rats. U0126 decreased withdrawal responses to mechanical stimulation of the whisker pad compared with U0124-treated rats. Because the secondary allodynia in V2 after inflammation in V3 was reduced by antagonizing ERK activation in the periphery, these data suggest a peripheral component to secondary allodynia mediated through ERK activation.     

海藻提取物对实验性高脂大鼠模型的药效学研究

目的：观察海藻提取物对实验性高脂血症大鼠模型的降脂和抗氧化作用。方法：取６０只雄性ＳＤ大鼠，分６组，除对照组外，无喂高脂饲料。给药组同时还以灌胃给药，第１７天取血，测定各组血清中的ＴＣ，ＴＧ，ＨＤＬ，ＭＤＡ和ＳＯＤ。结果：实验结果表明，与高脂模型组比较，海藻提取物组的ＴＣ，ＴＧ和ＭＤＡ水平降低，而ＨＤＬ和ＳＯＤ的水平增高，且有显著差异。     

The mucosal immune system in IgA nephropathy

Summary: IgA nephropathy is a clinically and histologically defined syndrome of unknown aetiology, which may have various causes in different parts of the world. Immunologically it is characterized by deposition of IgA1, probably polymeric IgA, in the mesangium and is frequently associated with IgG, C3 and components of the alternative pathway of the complement cascade. the disease can go into complete remission in children, but in adults it usually has a progressive course, characterized by the appearance of proteinuria and hypertension and loss of glomerular filtration rate (GFR). Histologically the development of glomerulosclerosis and tubulo-interstitial changes correlate with a clinical progressive course. the mucosal immune system is characterized by high plasma IgAl antibody responses after parenteral immunization with viral or bacterial vaccines. However, following nasal challenge with a bacterial neoantigen, IgA nephropathy patients appear to have a defective mucosal immune response in their nasal washes, in their bone marrow and in their plasma IgA1 antibody levels.     

Age-related changes in perception of support surface inclination during quiet stance

The ability to detect that a support surface is level, based upon individual concept of verticality and normal ankle angle during quiet stance, was studied in 11 elderly and 11 young subjects. In response to initial displacement of the tilt platform within a ± 4° range, subjects returned their support surface to level using a hand-held control switch. All sensory inputs regarding the actual platform position were available except direct visual feedback. The task was performed both with eyes open and eyes closed, with both feet on the platform. Elderly subjects exhibited a positive 0.9° shift of the subjective level compared with absolute level, in contrast to young subjects whose subjective level differed from absolute level by not more than 0.25°. There were no significant within-group differences between the eyes open and eyes closed conditions; however, positive shift of the subjective level persisted in the elderly group. The observed shift might be related to a compensatory strategy for overcoming the age-related decline in postural stability in old adults.     

Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome

Abstract:  We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30-year-old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1-h graft biopsy after reperfusion showed thin basement membrane disease. We re-tested the patient's native kidney biopsy specimen by immunohistochemical staining using α-chain-specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV α3-, α4- and α5-chain on glomerular basement membrane, but positive staining of α5-chain on Bowman's capsular basement membrane was noted. A diagnosis of autosomal-recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end-stage renal disease and the other thin basement membrane disease.