Chaos and control in mass-action binding of endogenous compounds

Endogenous compounds, such as hormones and neurotransmitters, interact with cellular receptors in controlled reactions governed by the mass-action law. Autoreceptors, a subset of the receptor pool, when activated by the endogenous ligand, result in a negative feedback that reduces the further release of ligand. This paper discusses and illustrates this control system when the concentrations (free and bound) are near or slightly beyond the limits of effective feedback control. Specifically, a forced periodic input function, simulating periodic release of the ligand, is used in the simulation of this controlled binding reaction in which a parameter representing the upper limit of control is varied. The solution of the system differential equations, representing free and bound ligand, is shown to pass from periodic to chaotic as the parameter is varied.     

Possible coumarin-like mechanism of action for cephalosporins

Summary In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K₁ was injected to investigate whether this was followed by an increase in vitamin K₁ 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K₁-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K₁-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K₁-epoxide plasma concentrations following injection of 10 mg vitamin K₁, whereas in normal subjects only traces of K₁-epoxide could be detected (<0.030 µg/ml). The K₁-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 µg/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K₁-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.Abbreviation PT prothrombin time - TT thrombin time - PTT partial thromboplastin time - PC platelet count - ICU intensive care unit - EEG electroencephalogram - K₁-epoxide vitamin K₁ 2,3-epoxide     

幽门螺杆菌疫苗免疫机制的研究进展

幽门螺杆菌(H.pylori)是定植于人体胃粘膜的重要致病菌,而粘膜疫苗以其有效的保护性免疫成为防治H.pyiori的热点,但对相应的免疫机制的认识目前尚不明确.故本文对H.pyiori疫苗的保护性免疫机制中的抗原递呈机制,抗体的作用以及TH细胞反应的作用等研究进展做一概要介绍.     

The early phase of experimental acute renal failure

Experiments were conducted to establish whether diminished solute reabsorption in the loop of Henle during acute renal failure could explain the loss of urinary concentration and participate in generating a tubuloglomerular feedback-mediated reduction in filtration rate. The electrolyte content of the fluid in the ascending limb of the loop of Henle was determined in situ by monitoring its electrical conductivity after propulsion into the distal tubule with a sudden burst perfusion. The value of the minimum electrolyte concentration decreased exponentially with increasing equilibration time, reaching a steady-state value equivalent to 27±9 mM NaCl in normal kidneys, 34±15 mM in mercuric chloride kidneys and 53±22 mM following ischaemia. A mathematical model was derived to describe the process of sodium chloride dilution from which it was possible to calculate both the permeability and transport velocity of the cortical thick ascending limb. In the normal kidney, the transport velocity was calculated to be 4.65±0.92 ·10^–5 cm/s, a value not significantly different from that of the mercuric chloride or ischaemic kidneys, and the estimated permeability was 1.13±0.52·10^–5 cm/s, not different from that of the mercuric chloride kidneys but significantly lower than that calculated for the ischaemic kidneys. It is concluded that for the more severely damaged ischaemic model, the loss of urinary concentrating ability was accompanied by a reduction in diluting ability of the ascending limb of the short loop of Henle, which appears to be due, at least in part, to an elevation of the passive permeability to sodium chloride in this segment.     

人格特征与防御方式的相关研究

目的 :尝试用防御机制解释EPQ各维度的特征。方法 :采用EPQ人格问卷、DSQ防御方式问卷、16PF中的G量表对 2 2 0例成人进行测试。结果 :本样本中EPQ各维度与成熟防御方式均无显著相关 (P >0 .0 5 ) ,N维度和P维度均与不成熟防御方式、中间型防御方式有显著正相关 (P <0 .0 0 1)。结论 :本研究显示 ,可以用防御机制解释EPQ各维度的某些特征。     

Adaptive motor unit action potential clustering using shape and temporal information

An adaptive algorithm is described that groups motor unit action potentials (MUAPs), detected in a composite EMG signal during signal decomposition, and creates partial motor unit action potential trains (MUAPTs). Data-driven MUAP shape and motor unit firing-pattern based criteria are used to form the clusters. An algorithm for estimating MUAPT temporal parameter, which provides accurate estimates even for partially defined trains, is used to obtain firing-pattern information. No a priori knowledge is required regarding the number of clusters or the distribution of their template shapes. The clustering algorithm when applied to real concentric-needle detected MUAP data provides accurate and useful clustering results. Compared to a classical leader-based algorithm, it provides more robust performance, is better able to estimate the true number of motor units represented in a set of detected MUAPs, and obtains more complete and accurate MUAPTs.     

Rapid non-genomic inhibitory effects of glucocorticoids on human neutrophil degranulation

Background: Glucocorticoids acting as anti-inflammatory or immunosuppressive drugs have been shown to exert most of their effects genomically. Recent findings suggest that non-genomic activity might be relatively more important in mediating the therapeutic effects of high-dose pulsed glucocorticoid. However, few non-genomic anti-inflammatory effects were reported, much less non-genomic mechanisms.Objective: This study was performed to investigate the nongenomic effects of glucocorticoids on human neutrophil degranulation.Methods: Purified human neutrophils were pretreated with 6 -methylprednisolone or hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10^–6 M) or phorbol myristate acetate (PMA) (50 ng/ml) in the presence of cytochalasin B. The release of two markers of neutrophil granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology methods respectively.Results: Both 6 -methylprednisolone (10^–5–10^–4 M) and hydrocortisone (10^–4 M) showed significant inhibitory effects on neutrophil degranulation within 5 min after fMLP administration. For PMA stimulated degranulation, 6 -methylprednisolone (10^–4 M) showed significant inhibitory effects (p < 0.01), while hydrocortisone (10^–4 M) only showed an inhibitory tendency (P > 0.05). Neither RU486 (10^–5 M) nor cycloheximide (10^–4 M) could alter the inhibitory effects of glucocorticoids.Conclusion: Our results demonstrate that megadoses of glucocorticoids exert rapid inhibitory effects on human neutrophil degranulation at the cellular level via a new mechanism that is independent of corticosteroid type II receptor occupation or protein synthesis. We infer that these effects may be very important when glucocorticoids act as anti-inflammatory drugs during pulse therapy.Received 20 May 2004; returned for revision 21 July 2004; accepted by M.J. Parnham 23 September 2004L. Liu and Y. X. Wang contributed equally to this work.     

齿龈内阿米巴的致病作用与致病机制的研究

在注射免疫抑制剂 1周后的大白鼠龈缘涂抹齿龈内阿米巴 (Emtamoebagingivalis ,E .g .) ,5天后 ,牙龈组织出现溃疡、牙周脓肿形成、脓液查见活E .g .、牙槽骨吸收等牙周炎病症。电镜术与生化分析发现 :E .g .伪足活跃、有丰富的溶酶体 ,所含水解酶与ACP显著较健康组高 (P <0 0 1) ,可使牙周组织溶解与受损。SOD较健康组显著性低 (P <0 0 1) ,MDA显著性增高 (P <0 0 1) ,说明E .g .感染产生较多氧自由基可使细胞膜受损 ,加上口腔共生菌的协同作用使免疫力低下的宿主发生牙周炎。     

Effect of C-peptide administration on whole body glucose utilization in STZ-induced diabetic rats

Recent studies suggest that C-peptide stimulates glucose transport in isolated skeletal muscle. In order to determine the effect of C-peptide on whole body glucose utilization, streptozotocin (60 mg kg^-1) (STZ)-induced diabetic and normal rats were studied using the euglycaemic clamp procedure and continuous infusion of somatostatin (1.0 μg kg^-1 min^-1) in pentobarbital-anaesthetized rats. Plasma insulin levels during the 6.0- and 30.0-mU kg^-1 min^-1 insulin infusions rose to 70–90 μU mL^-1 and 500–700 μU mL^-1, respectively. Blood glucose concentrations were clamped at 7.5–7.9 mmol L^-1 in the diabetic rats and at basal levels or 7.7 mmol L^-1 in the non-diabetic (normal) rats. Biosynthetic human C-peptide (0.5 nmol kg^-1 min^-1) was infused in 12 diabetic and 11 normal rats, resulting in concentrations of 26–41 nmol L^-1. The metabolic clearance rate of glucose (MCR) for the diabetic rats receiving C-peptide (12.0±1.0 mL kg^-1 min^-1) was significantly (P<0.01) higher than that in the diabetic rats given saline (6.3±0.7 mL kg^-1 min^-1) or a randomly scrambled C-peptide (7.8±1.3 mL kg^-1 min^-1) at low-dose insulin infusion but not at the high-dose insulin infusion. In normal rats C-peptide did not significantly increase the MCR for glucose. These results thus demonstrate that C-peptide has the capacity to increase glucose utilization in STZ-induced diabetic rats.