Both the antioxidant and D3 agonist actions of pramipexole mediate its neuroprotective actions in mesencephalic cultures

Pramipexole (PPX) is a full intrinsic activity, direct-acting dopamine (DA) agonist possessing 7-fold higher affinity for D3 than for D2 receptors. It also is a potent antioxidant. PPX was previously shown to be neuroprotective because it dose dependently attenuated the DA neuron loss produced by levodopa in mesencephalic cultures. Several different drugs with properties similar to PPX were studied here to better understand the mechanism or mechanisms responsible for this neuroprotective effect. The D3-preferring agonist 7-hydroxy-diphenylaminotetralin (7-OH-DPAT) and the D3 antagonist U99194, respectively, increased and decreased the neuroprotective effects of PPX in a dose-dependent fashion. Addition of the selective D2 agonist U95666 or the D2/D3 antagonists domperidone or raclopride did not affect PPX's neuroprotective effect. Interestingly, 7-OH-DPAT by itself did not attenuate the DA neuron loss produced by levodopa. However, when 7-OH-DPAT was combined with a low dose of the antioxidants U101033E or alpha-tocopherol, the toxic effects of levodopa were attenuated. Similar results were observed when the D3-preferring agonist PD128, 907 was studied. In addition, media conditioned by exposure of mesencephalic cultures incubated with all D3-preferring agonists studied was shown to enhance the growth of DA neurons in freshly harvested recipient cultures implicating a D3-mediated trophic activity in the neuroprotective effect. These data suggest that PPX's neuroprotective actions in the levodopa toxicity model are a consequence of its combined actions as a D3 receptor agonist and an antioxidant.     

蝶腭,筛前神经及鼻甲联合手术治疗常年性变应性鼻炎

在鼻内窥镜下为４０例行蝶腭、筛前神经及鼻甲联合手术治疗常年性变应性鼻炎。结果：术后１月全部患者症状消失,显效１００％;术后１年显效３３例,占８２．５％;有效６例,占１５％,有效率为９７．５％。提示该方法可广泛阻滞鼻腔副交感神经来源,降低鼻粘膜感觉灵敏部位敏感性以及感觉—副交感神经反射,破坏喷嚏反射弧的传入通路,使鼻粘膜对外界刺激敏感性下降,血管扩张减轻,腺体分泌减少,对常年性变应性鼻炎有明显疗效。     

抗A1试剂血清的研制

目的 :ABO亚型在临床输血中经常造成错定血型及输血反应 ,因而研制抗A1试剂血清是解决ABO亚型鉴定的主要途径。方法 :采用血型血清学特异性抗原抗体吸收实验。结果 :经大量反复实验 ,研制出特异性强 ,效价符合要求的抗A1试剂血清。结论 :抗A1血清是鉴定A亚型的专用试剂血清 ,对临床鉴定ABO亚型及安全输血有实用意义。     

3种低温保存板层角膜移植材料的电镜观察

评价低温保存板层角膜移植材料的效果。方法将１５只人尸角膜分三组保存２年：４℃甘油脱水法,角膜液氮冷冻法,全眼球液氮冷冻法。并做透射电镜观察。结果第一组中,角膜胶原纤维排列紊乱,疏松,缺乏连续性,可见广纤维变性,纤维间可见极低电子密度灶。     

Incomplete cement mantles in the sagittal femoral plane: an anatomical explanation

The influence of operative technique on the formation of incomplete cement mantles in the sagittal plane has been rarely considered in the literature. In this article, we discuss the influence of the anatomy of the proximal femur on the formation of incomplete cement mantles and discuss how their incidence can be reduced by correct component positioning.     

Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex

Summary The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E₁ component, specifically due to mutations in the X-linked E₁ gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X-inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3 end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin-responsiveness of the enzyme and the patient's clinical symptoms.Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross-reactive to pyruvate carboxylase antibody is present in cultured cells (CRM^+ve). In the latter group, cross-reacting material is rarely present (CRM^–ve). The CRM^+ve patients can survive into teenage years with careful supervision, while the CRM^–ve patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.     

SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: ANGIOTENSIN II-INDUCED TYROSINE PHOSPHORYLATION IN MESANGIAL AND VASCULAR SMOOTH MUSCLE CELLS

• 1 Angiotensin II (AngII)-induced, activation of phospholipase C (PLC) and Ca²⁺-dependent Cl^? channels is an important signal transduction pathway for the regulation of vascular smooth muscle cell (VSMC) and glomerular mesangial cell contraction and growth. While AT receptors are traditionally thought to be G-protein coupled to the β isoform of PLC, recent evidence suggests that in some tissues AT receptors may also activate the PLC-γ isoform via tyrosine phosphorylation.
• 2 By western analysis, we identified PLC-γ1 in the above cell types. We found that within 3 min of exposure to 10^?7 mol/L AngII, tyrosine phosphorylation of PLC-γ1 was observed; however, peak response (> 3-fold increase) occurred within 0.5 min. In addition, pre-incubation of these cells with the tyrosine kinase inhibitor genistein blocked the tyrosine phosphorylation of PLC-γ1 by AngII. In contrast, preincubation with the tyrosine phosphatase inhibitor sodium vanadate increased the levels of tyrosine phosphorylation of PLC-γ1. Similar results were found when intracellular levels of 1,4,5-IP₃ were measured after AngII exposure.
• 3 By using patch clamp techniques on cultured rat mesangial cells exposed to AngII, we found that the release of 1,4,5-IP₃-sensitive intracellular Ca²⁺ stores stimulated low conductance Cl^? channels. Preincubation with genistein, abolished the usual 10-fold increase in Cl^? channel activity observed with AngII.
• 4 Therefore, we conclude that in VSMC and glomerular mesangial cells (i) AngII transiently stimulates PLC activity via tyrosine phosphorylation of the γ1 isoenzyme, (ii) tyrosine phosphorylation of PLC-γ1 and production of 1,4,5-IP₃ in response to AngII is dramatically inhibited by tyrosine kinase inhibition and stimulated by tyrosine phosphatase inhibition, (iii) activation of Ca²⁺-dependent Cl^? channels by AngII-induced release of 1,4,5-IP₃-dependent intracellular Ca²⁺ stores is also abolished by tyrosine kinase inhibition. In summary, this AngII-induced signal transduction cascade provides a possible mechanism for both the contractile and growth-stimulating effects of AngII on VSMC and glomerular mesangial cells.

     

Effects of eating an uncooked vegetable diet for 1 week

Biochemical and metabolic indicators were monitored in a group of volunteers suffering from a variety of chronic illnesses participating in a week's course on a special uncooked vegetable diet, known as "living food". Unmatched healthy controls ate the same diet cooked for 2 min in a microwave oven. After 1 week on the regimen, serum protein and urea contents decreased and alanine aminotransferase (ALAT) activity increased in both groups, although all within the normal range. Blood glucose increased in both groups to slightly above normal limits but total serum cholesterol dropped about 1 mmol/l from normal starting levels. Serum tocopherol and retinol increased only in the group eating the uncooked diet. In both groups urinary sodium dropped drastically without a significant change in potassium. Serum and urinary phenol and p-cresol diminished also significantly. It is concluded that this vegetable diet may be of some benefit in the short term but any longer-term use requires evaluation.     

早期小剂量多巴胺治疗新生儿缺氧缺血性脑病

目的　观察早期应用小剂量多巴胺治疗新生儿缺氧缺血性脑病 (HIE)的疗效。方法　在常规治疗基础上 ,治疗组患儿早期应用多巴胺 5μg·kg- 1 ·min- 1 静脉滴注。结果　治疗组疗效显著优于对照组 ,P<0 0 1 ,治疗组患儿治疗 5～ 7d后全部痊愈出院。结论　早期应用小剂量多巴胺治疗新生儿缺氧缺血性脑病可降低病死率 ,缩短疗程