Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study.

Upper limb weakness following a stroke affects 80% of survivors and is a key factor in preventing their return to independence. State-of-the art approaches to rehabilitation often require that the patient can generate some activity in the paretic limb, which is not possible for many patients in the early period following stroke. Approaches that enable more patients to engage with upper limb therapy earlier are urgently needed. Motor imagery has shown promise as a potential means to maintain activity in the brain's motor network, when the patient is incapable of generating functional movement. However, as imagery is a hidden mental process, it is impossible for individuals to gauge what impact this is having upon their neural activity. Here we used a novel brain-computer interface (BCI) approach allowing patients to gain an insight into the effect of motor imagery on their brain-muscle pathways, in real-time. Seven patients 2-26 weeks post stroke were provided with neurofeedback (NF) of their corticospinal excitability measured by the size of motor evoked potentials (MEP) in response to transcranial magnetic stimulation (TMS). The aim was to train patients to use motor imagery to increase the size of MEPs, using the BCI with a computer game displaying neurofeedback. Patients training finger muscles learned to elevate MEP amplitudes above their resting baseline values for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. By day 3 for ADM and day 4 for FDI, MEP amplitudes were sustained above baseline in all three NF blocks. Here we have described the first clinical implementation of TMS NF in a population of sub-acute stroke patients. The results show that in the context of severe upper limb paralysis, patients are capable of using neurofeedback to elevate corticospinal excitability in the affected muscles. This may provide a new training modality for early intervention following stroke.

[Study on diagnosis and treatment of infections multiple organ dysfunction syndrome by integrated traditional Chinese and Western medicine].

OBJECTIVE: To explore the diagnostic and therapeutic approach of integrated traditional Chinese and western medicine (TCM-WM) on infectious multiple organ dysfunction syndrome/multiple system and organ failure (MODS/MSOF) for elevating the successful rate of rescuing the patients. METHODS: Diagnosis with western medicine and Syndrome Differentiation of TCM in 225 in-patients of acute infectious disease complicated with MODS/MSOF were conducted, and TCM treatment, based on western medical comprehensive treatment, was given to observe the effect and explore the mechanism of the TCM-WM therapy. RESULTS: Up to the end of 1998, 161 cases of the 225 cases were successfully cured and 64 died, the mortality being 28.4%. Among them, 58 out of 140 cases of MSOF died, the mortality was accounted for 41.4%. In 106 cases conformed to the diagnostic criteria of MSOF proposed by Professor Knaus WA, USA, 52 cases were cured successfully and 54 died, the mortality being 50.9%. CONCLUSION: TCM-WM treatment could elevate the therapeutic effect in treating MODS, the mechanism might be through improving the hemodynamic and hemorrheologic condition of patients to relieve nail-fold microcirculation disorder; influencing the levels of cytokine and inflammatory mediator, so as to alleviate the systemic inflammatory reaction, it might also abate the inhibited condition of gastro-intestinal motility, alleviate the intestinal flora imbalance, prevent intestinal bacteria and endotoxin malposition, and protect cells from peroxidation.

Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation.

We have cloned a cDNA encoding the full-length coding region of the human homologue of the germ cell nuclear factor (GCNF)/retinoid receptor-related testis-associated receptor (RTR), from a human testis cDNA library. The amino acid sequence of human GCNF/RTR is highly homologous to that of the mouse GCNF/RTR. The largest difference between the two homologues is a 15 amino acid deletion in the human GCNF/RTR at amino acid 47. The GCNF/RTR gene was localized on human chromosome 9. Northern blot analysis using poly(A)+ RNA from different human tissues showed that GCNF/RTR mRNA is most abundantly expressed in the testis. GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives. Induction of differentiation of mouse embryonal carcinoma F9 cells and human embryonal carcinoma NTERA-2 clone D1 (NT2/D1) cells by all-trans retinoic acid was accompanied by a down-regulation of GCNF/RTR. Our observations suggest that GCNF/RTR plays a role in the control of gene expression in early embryogenesis and during spermatogenesis.

Lipofectin-facilitated transfer of cholecystokinin gene corrects behavioral abnormalities of rats with audiogenic seizures.

To evaluate the potential for lipofectin-mediated central nervous system gene transfer, the plasmid coding for cholecystokinin was administered intracerebroventricularly to rats, which have congenital audiogenic seizures and high responses to peripheral electric stimulation-induced analgesia. Previous studies had shown that low brain cholecystokinin levels may be the neurochemical variable of rat's audiogenic seizure and high responses to the analgesia because cholecystokinin is an anticonvulsant and anti-opioid neuropeptide. Gene transfer of cholecystokinin corrected the increased susceptibility to audiogenic seizures and the high responses to analgesia for about one week. Similar administration of plasmid expressing beta-galactosidase indicated that the vector mainly transfected ependymal cells lining the ventricle and pia mater cells. The increased cholecystokinin messenger RNA and immunoreactivity in the hippocampus following stereotactic intrahippocampal administration of cholecystokinin plasmid was also demonstrated with in situ hybridization and immunohistochemistry techniques. These results suggest that lipofectin-mediated gene transfer will be useful for studies of brain function, the modification of behavior and gene therapy for central nervous system disorders.

Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

Acyl secoiridoids and antifungal constituents from Gentiana macrophylla.

LC-UV-mass spectrometry and bioassay co-directed fractionation of an aqueous acetone extract of the roots of Gentiana macrophylla gave three new chromene derivatives and two novel and six known secoiridoids, along with kurarinone, kushenol I, beta-sitosterol, stigmasterol, daucosterol, beta-sitosterol-3-O-gentiobioside, alpha-amyrin, oleanolic acid, isovitexin, gentiobiose and methyl 2-hydroxy-3-(1-beta-D-glucopyranosyl)oxybenzoate. The structures of the new products were established from spectral and chemical evidence as 2-methoxyanofinic acid and macrophyllosides A-D. The six known secoiridoids were gentiopicroside, sweroside, 6'-O-beta-D-glucosylgentiopicroside, 6'-O-beta-D-glucosylsweroside, trifloroside and rindoside. The new acid (2-methoxyanofinic acid), its methyl ester, kurarinone and kushenol I were shown to be active against the plant pathogenic fungus Cladosporium cucumerinum. The methyl ester and kurarinone inhibited also the growth of the human pathogenic yeast Candida albicans. Structure-activity relationships were studied. Thus, addition of a methoxyl group to the benzene nucleus of anofinic acid (2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid) increased the antifungal activity remarkably whereas glycosylation at the carboxylic moiety was found to remove the activity. Esterification of the new acid induced its activity against C. albicans, but decreased its growth inhibition properties against C. cucumerinum. Hydroxylation of kurarinone at the 3 beta-position removed its activity against C. albicans and decreased the inhibition of C. cucumerinum. In addition, the chemotaxonomic significance of the identified constituents is discussed.

Secoiridoids and antifungal aromatic acids from Gentiana algida.

Fractionation of an aqueous acetone extract of the whole herb of Gentiana algida gave one new [2'-(o,m-dihydroxybenzyl)sweroside] and five known secoiridoids, together with anofinic acid, fomannoxin acid, sitosterol, daucosterol, stigmasterol, oleanolic acid, orientin and gentianose. The structures were determined by spectral methods and a few chemical transformations. Anofinic acid and fomannoxin acid were found to be active against Cladosporium cucumerinum, a plant pathogenic fungus. Preliminary structure-activity studies indicated that the presence of carboxylic moieties in these acids was presumably a precondition for activity, whereas their methyl esters, inactive to the fungus, were active against the human pathogenic yeast Candida albicans. The chemotaxonomic significance of the isolates is discussed briefly.

Effects of micronutrients and antioxidants on lipid peroxidation in human plasma and in cell culture.

Plasma levels of triglycerides, retinol, cholesterol, lipid-phase antioxidants (alpha-, gamma-tocopherols, beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin and lutein/zeaxanthin), and thiobarbituric acid-reactive substances (TBA-RS), as an indicator of lipid peroxidation, were repeatedly determined in nine individuals over a 3-month period. Levels of TBA-RS were positively correlated with plasma triglycerides and gamma-tocopherol, and negatively correlated with plasma carotenoids. These results were consistent with in vitro cell culture studies which showed increased TBA-RS for cells supplemented with linolenic acid and decreased levels when treated with beta-carotene. We conclude that TBA-RS measurements in plasma accurately reflect the level of peroxidizable substrate as modified by the presence of a variety of dietary antioxidants, particularly carotenoids. Although the inter- and intra-individual variabilities for TBA-RS are comparable with the micronutrients and antioxidants measured in this study, high interassay variability and the strong association with the more commonly measured plasma triglycerides suggest the TBA-RS assay to be of limited use in epidemiologic studies. However, this assay does appear to be useful in cell culture studies where experimental conditions can be better controlled. Low ratios of inter- to intra-individual variability in some of the plasma micronutrient and lipid-phase antioxidants measured suggest that multiple samples may be required to characterize individuals in studies evaluating the relation between these plasma constituents and disease incidence.

[Effect of Japanese Ganoderma Lucidum on production of interleukin-2 from murine splenocytes].

The purpose of this study was to determine the effect of Ganoderma lucidum (GL) planted in Japan on the production of Interleukin-2 (IL-2) from murine splenocytes. It was observed that hydrocortisone (HC) 0.025-1 microgram /ml could significantly antagonize the inhibitory activity of HC and CSA to increase the production of IL-2 in vitro, P < 0.01. When the splenocytes pretreated with GL alone or in combination with HC, it was shown that pretreatment alone had no significant effect on IL-2 production, but preincubating splenocytes with HC and GL resulted in a significant increase of IL-2 production when compared with that of HC group, P < 0.01. In vivo, GL 300 mg/kg could increase the production of IL-2 when oral taken GL alone or in combination of HC.

[Immunosuppressive and antiinflammatory activities of tripterine].

Tripterine is one of the active components isolated from Tripterygium wilfordii Hook.f. In this study tripterine was shown to inhibit the antibody response of mouse splenocytes to SRBC both in vitro and in vivo either by primary or secondary stimulation. Tripterine was also found to significantly inhibit cotton pellet induced granuloma growth in rats and depress the delayed hypersensitive reaction of mouse skin to dinitrochlorobenzene (DNCB). Besides, it also increased the sleeping time of mouse induced by pentobarbital sodium. From the results stated above, it appears that tripterine might be useful in the treatment of inflammatory diseases or autoimmune diseases.

[Determination of the contents of mineral elements in the soil where the jinin big-wild ginseng grows].

The element contents in the soil where the Jilin Big-Wild Ginseng grows were determined with plasma emission spectrometry. 23 elements in the soil were found, of which 12 are macro and trace elements indispensable to Ginseng growth. This study provides a scientific basis for selecting suitable soil for planting wild ginseng, or for creating optimum soil conditions for the bumper harvest and high quality of Ginseng.