Effects of arginine, S-adenosylmethionine and polyamines on nerve regeneration

Introduction - Axon growth and axon regeneration are complex processes requiring an adequate supply of certain metabolic precursors and nutrients. Material and methods - This article reviews the studies examining some of the processes of protein modification fundamental to both nerve regeneration and to the continuous and adequate supply of specific factors such as arginine, S-adenosylmethionine and polyamines. Results - The process of arginylation notably increases following nerve injury and during subsequent regeneration of the nerve, with the most likelyfunction of arginine-modification of nerve proteins being the degradation of proteins damaged through injury. It appears that defective methyl group metabolism may be one of the leading causes of demyelination, as suggested by the observation of reduced cerebrospinal fluid concentrations of s-adenosylmethionine (SAMe) and 5-methyltetrahydrofolate, the key metabolites in methylation processes, in patients with a reduction in myelination of corticospinal tracts. Polyamine synthesis, which depends strongly on the availability of both SAMe and arginine, markedly increases in neurons soon after an injury. This "polyamine-response" has been found to be essential for the survival ofthe parent neurons after injury to their axons. Polyamines probably exert their effects through involvement in DNA, RNA and protein synthesis, or through post-translational modifications that areindicated as the most relevant events of the "axon reaction." Conclusions - Nerve regeneration requires the presence of arginine, s-adenosylmethionine, and polyamines. Further studies are needed to explore the mechanisms involved in these processes.     

High β-adrenoceptor density on peripheral blood mononuclear cells in progressive multiple sclerosis: a manifestation of autonomic dysfunction?

In multiple sclerosis (MS) up-regulation of β-adrenoceptors on peripheral blood mononuclear cells (PBMCs) has been attributed to either autonomic dysfunction, inflammation or a combination of the two. We have compared secondary progressive MS patients with normal subjects (NS) and two models of autonomic dysfunction; pure autonomic failure (PAF) and multiple system atrophy (MSA, Shy-Drager syndrome). There was up-regulation of β-adrenoceptors on PBMCs in MS and PAF patients but not in MSA patients. Only in PAF patients β-adrenoceptor up-regulation was correlated with low plasma levels of noradrenaline (NA) and adrenaline (Ad). In addition to studies in the basal state, measurements also were made after the centrally acting sympatholytic agent clonidine. These were combined with haemodynamic and neurohormonal measurements. After clonidine, there was a fall in blood pressure in NS and MSA patients but not in MS and PAF patients; a rise in growth hormone (GH) in NS and PAF patients but not in MS and MSA patients; and an up-regulation in PBMCs β-adrenoceptors in NS but not in MS, MSA and PAF patients. Up-regulation of β-adrenoceptors on PBMCs in MS could be attributed to autonomic dysfunction but the disparity between MS and PAF patients when considering their plasma levels of NA and Ad argue against. Although the neurohormonal responses to clonidine and the physiological assessment of autonomic function in progressive MS patients, demonstrate central autonomic dysfunction resembling that of the MSA patients, the normal basal β-adrenoceptor densities in the latter, suggests that the up-regulation of these receptors is independent of the central autonomic dysfunction in MS.     

S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies

Introduction - S-adenosyl-l-methionine (SAMe) is a naturally-occurring substance which is a major source of methyl groups in the brain. Material and methods - We conducted a meta-analysis of the studies on SAMe to assess the efficacy of this compound in the treatment of depression compared with placebo and standard tricyclic antidepressants. Results - Our meta-analysis showed a greater response rate with SAMe when compared with placebo, with a global effect size ranging from 17% to 38% depending on the definition of response, and an antidepressant effect comparable with that of standard tricyclic antidepressants. Conclusion - The efficacy of SAMein treating depressive syndromes and disorders is superior with that of placebo and comparable to that of standard tricyclic antidepressants. Since SAMe is a naturally occurring compound with relatively few side-effects, it is a potentially important treatment for depression.     

The extracellular matrix of cartilage in the growth plate before and during calcification: Changes in composition and degradation of type II collagen

Summary Calcification occurs in the extracellular matrix of the hypertrophic zone of the growth plate when the extra-cellular matrix volume is reduced to a minimum and alkaline phosphatase content is maximal. The present study shows that significant quantitative and qualitative changes occur in the composition and structure of macromolecules in the extracellular matrix before and during calcification in the proximal tibial growth plate of the bovine fetus. These were detected in part by using microchemical and microimmuno-chemical analyses of sequential transverse frozen sections at chemical analyses of sequential transverse frozen sections at defined sites throughout the growth plate. Concentrations of matrix molecules in the extracellular matrix have not previously been determined biochemically. They were measured per unit matrix volume by using combined immunochemical/chemical-histomorphometric analyses. The concentrations within the extracellular matrix of the C-propeptide of type II collagen, aggregating proteoglycan (aggrecan), and hyaluronic acid all progressively increased in the maturing and hypertrophic zones, being maximal (or near maximal) at the time of initiation of mineralization. These results for proteoglycan are contrary to some earlier reports of a loss of proteoglycan prior to mineralization which measured the tissue content of proteoglycan rather than that present in the extracellular matrix, the volume of which is progressively reduced as the growth plate matures. The C-propeptide data provides a quantitative confirmation of previous immunohistochemical studies. Total collagen concentration (measured as hydroxyproline) in the extracellular matrix initially increased through the proliferating and maturing zones but then rapidly decreased in the hypertrophic zone. Immunohistochemical studies revealed that this is associated with the unwinding of the triple helix of type II collagen (previously shown to result from cleavage) which starts in pericellular sites in the zone of maturation (when type X collagen is first synthesized) and then extends throughout the hypertrophic zone. The significance of these matrix changes in the development and mineralization of the growth plate is discussed.     

刺五加叶皂甙单体Sb对培养大鼠心肌细胞动作电位的影响

本研究中所用的刺五加叶皂甙单体Ｓｂ（５０、２００μｇ／ｍＬ），使培养的ｗｉｓｔａｒ大鼠心肌细胞动作电位的波幅、波宽、阈电位、最大舒张电位、超射、最大除极速度及复极（１０％、５０％、９０％）水平的动作电位波宽一致减小。Ｃａ２＋８０μｇ／ｍＬ能使之反转，Ｓｂ作用与尼莫地平作用相似。上述结果表明Ｓｂ具有钙通道阻滞作用。     

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe): presentation with a puzzling penile plaque*

Objective Report of two cases of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), with typical penile lesions. Differential diagnosis of persistent penile plaques. Background Following remission of the generalized eruption of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), it is not unusual to see a single remaining lesion localized on the penis. Since Sulzberger et al. (Sulzberger MB, Witten VH, Hunt JA. Puzzling persistent penile plaques. Arch Dermatol 1956:73:101-109) reviewed dermatoses presenting with puzzling persistent penile plaques in 1955, further dermatoses have evolved as important differential diagnoses. Much controversy has arisen as to the justification of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe) as a disease entity. Conclusions Diagnosis of most cases of persistent plaques of dermatitis on the penis is possible with a careful examination of the entire skin, and a thorough history to discover past lesions. The possibility of malignancy makes a biopsy mandatory. Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe) typically responds well to systemic steroids. Intrale-sional triamcinolone acetonide has been demonstrated to be effective in the treatment of a persistent penile plaque in exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), and may be helpful in discontinuing or reducing systemic therapy to a level compatible with long-term treatment.     

电针足三里穴对人体幽门运动功能影响的研究

应用内镜测压术,检测电针足三里穴前后部分健康成人和胃、十二指肠疾病患者幽门括约肌压力参数变化。结果表明:电针足三里穴对幽门括约肌压力波参数的影响主要表现为升高低振幅波和降低高振幅波,与电针非经穴点的单纯抑制效应有显著区别。提示电针足三里穴有兴奋和抑制幽门括约肌功能的双相调节效应。     

系统性红斑狼疮肺胸膜病变(附50例报告)

50例SLE患者有肺胸膜病变,其中女性47例(94％),男性3例(6％),小于40岁者41例(82％)。50例中表现为胸膜炎和(或)胸腔积液26例,狼疮肺炎15例,弥漫性肺间质纤维化5例,肺不张3例,肺纹理增多17例。经激素治疗随SLE症状改善,肺胸膜病变好转。     

The Effect of 50 Hz External Electrical Interference on Implanted Cardiac Pacemakers

The effects of injected 50 Hz alternating current on the function of cardiac pacemakers has been observed in 18 patients with implanted unipolar VVI units. Current, in the range 0-600 microA was applied via electrodes attached to the patients' upper body and feet and fed from a specially designed current injection unit at the bedside. Most implanted pacemakers reverted to interference mode in the current range 29-250 microA. At current levels just below the reversion current all units developed irregular and inappropriate pacing. This current level was pacemaker dependent and varied in the range 27-246 microA. The total reversion current depended on the location of the injecting electrodes and on the patients' posture. The sensitivity of the units to injected interference was increased by deep inspiration. Temporary pacing catheters fitted to an additional ten patients were used to monitor the interference voltage which would be sensed by an implanted unit. This voltage was similarly dependent on patient posture and on deep respiration. Current injection has proved to be a safe, controllable and reproducible method of testing the sensitivity of implanted pacemakers to 50 Hz external interference.