Peripheral axotomy affects nicotinamide adenine dinucleotide phosphate diaphorase and nitric oxide synthases in the spinal cord of the rabbit

Using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry and nitric oxide synthase (NOS) immunocytochemistry combined with radioassay of calcium-dependent NOS activity, we examined the occurrence of NADPHd staining and NOS immunoreactivity (NOS-IR) in the dorsal root ganglia (DRG) neurons, dorsal root afferents, and axons projecting via gracile fascicle to gracile nucleus 14 days after unilateral sciatic nerve transection in the rabbit. Mild to moderate NADPHd staining and NOS-IR appeared in a large number of small and medium-sized to large neurons in the ipsilateral L4-L6 DRG, accompanied by enhanced NOS-IR of thick myelinated fibers in the ipsilateral L4-L6 dorsal roots. A noticeable increase in the density of punctate NADPHd staining occurred throughout laminae I-IV in the ipsilateral medial part of the dorsal horn in L4-L6 segments. Concurrently, a statistically significant decrease in the number of small NADPHd-exhibiting neurons in laminae I-II and, in contrast to this, a statistically significant increase of medium-sized to large NADPHd-stained somata in the ipsilateral laminae III-VI of L4-L6 segments were found. A detailed compartmentalization of L4-L6 segments into gray and white matter regions disclosed substantially increased catalytic NOS activity and inducible NOS mRNA levels in the dorsal horn and dorsal column ipsilaterally to the peripheral injury. A noticeable increase in the number of thick myelinated NADPHd-exhibiting and NOS-IR axons was noted in the ipsilateral gracile fascicle, terminating in dense, punctate NADPHd staining in the neuropil of the gracile nucleus. These observations indicate that the de novo-synthesized NOS in the lesioned primary afferent neurons resulting after sciatic nerve transection may be involved in an increase in NADPHd staining and NOS-IR in the ipsilateral dorsal roots and dorsal horn of L4-L6 segments, whence NOS could be supplied to ascending axons of the gracile fascicle.     

Modulation of Tumor Necrosis Factor-mediated Cell Death by Fullerenes

Purpose The fullerene (C₆₀/C₇₀ mixture—C_60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC_60/70) and polyhydroxylated C_60/70 [C_60/70(OH) _n ] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF). Materials and Methods TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes. Results THF/nC_60/70 augmented, while C_60/70(OH) _n reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC_60/70 or C_60/70(OH) _n . The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC_60/70 or C_60/70(OH) _n potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization. Conclusion The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.     

Sulfonamides as a subject to study molecular interactions in crystals and solutions: sublimation, solubility, solvation, distribution and crystal structure

Crystal structures of 4-amino-N-(4-chlorophenyl)-benzene-sulfonamide (IV), 4-amino-N-(2,3-dichlorophenyl)-benzene-sulfonamide (V), 4-amino-N-(3,4-dichlorophenyl)-benzene-sulfonamide (VI) and 4-amino-N-(2,5-dichlorophenyl)-benzene-sulfonamide (VII) were solved by X-ray diffraction method. Temperature dependencies of saturated vapour pressure and thermodynamic functions of sublimation process were calculated (IV: delta Gsub298=74.0 kJ mol(-1), delta Hsub298=134.1+/-1.2 kJ mol(-1), delta Ssub298=202+/-3 J mol(-1)K(-1); V: delta Gsub298=61.7 kJ mol(-1), delta Hsub298=141.1+/-0.7 kJ mol(-1), delta Ssub298=266+/-2 J mol(-1)K(-1); VI: delta Gsub298=85.8 kJ mol(-1), delta Hsub298=167.5+/-3.6 kJ mol(-1), delta Ssub298=274+/-8 J mol(-1)K(-1); VII: delta Gsub298=75.7 kJ mol(-1), delta Hsub298=155.4+/-1.6 kJ mol(-1), delta Ssub298=268+/-4 J mol(-1)K(-1)). Thermochemical parameters of fusion and evaporation processes for the compounds were obtained. Temperature dependencies of the solubility in water, n-octanol were measured. The thermodynamic functions of solubility and solvation processes were deduced. The transfer processes of the molecules from water to n-octanol were analysed by diagram method and main driven forces were established.     

Ribavirin ameliorates experimental autoimmune encephalomyelitis in rats and modulates cytokine production

To determine the mechanism underlying ribavirin induced amelioration of experimental autoimmune encephalomyelitis (EAE), cytokine profiles were evaluated in draining lymph node (DLN) cell culture supernatants and spinal cord obtained from EAE and/or ribavirin-treated EAE Dark Agouti rats. Administration of ribavirin to EAE rats markedly affected the production of pro-inflammatory cytokines IFN-gamma, IL-1beta and TNF-alpha in DLN and spinal cord, thus shifting the balance towards the anti-inflammatory cytokines IL-10 and TGF-beta. These findings suggest that ribavirin attenuates EAE by limiting cytokine-mediated immunoinflammatory events leading to CNS destruction. The conducted experiments provide rationale for ribavirin to be considered as a candidate drug in the development of new therapeutic strategies for the treatment of autoimmune diseases in humans, such as multiple sclerosis.     

LIME: a new membrane Raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling

Lymphocyte membrane rafts contain molecules critical for immunoreceptor signaling. Here, we report identification of a new raft-associated adaptor protein LIME (Lck-interacting molecule) expressed predominantly in T lymphocytes. LIME becomes tyrosine phosphorylated after cross-linking of the CD4 or CD8 coreceptors. Phospho-LIME associates with the Src family kinase Lck and its negative regulator, Csk. Ectopic expression of LIME in Jurkat T cells results in an increase of Csk in lipid rafts, increased phosphorylation of Lck and higher Ca2+ response to CD3 stimulation. Thus, LIME appears to be involved in regulation of T cell activation by coreceptors.     

Epidural oscillating field stimulation increases axonal regenerative capacity and myelination after spinal cord trauma

Oscillating field stimulation(OFS)with regular alterations in the polarity of electric current is a unique,experimental approach to stimulate,support,and potent...     

Transcranial Brain Parenchymal Sonography in Neurodegenerative and Psychiatric Diseases

Transcranial sonography is a highly sensitive noninvasive sonographic method for detection of early and specific echogenic changes in basal ganglia of patients with some neurodegenerative diseases. Transcranial sonography showed substantia nigra hyperechogenicity as a typical echo feature in idiopathic Parkinson disease and lenticular nucleus hyperechogenicity as a characteristic finding in atypical parkinsonian syndromes. Brain stem raphe hypoechogenicity or interruption has been shown to be highly prevalent in patients with unipolar depression as well as depression associated with certain neurodegenerative diseases. Transcranial sonography also revealed basal ganglia hyperechoic changes in movement disorders with trace metal accumulation such as Wilson disease, some entities of neurodegeneration with brain iron accumulation, as well as several forms of spinocerebellar ataxia. Transcranial sonography is a valuable neuro imaging method for early and differential diagnosis and follow‐up of patients with neurodegenerative and psychiatric diseases.     

Contribution of medullary raphé to control of coughing-Codeine trials in cat

In order to determine if a codeine-sensitive control system for cough exists in the medullary raphé four microinjections of codeine (3.3 and 16.5mM; 36.6±0.7nl 1.5 and 3mm rostral to the obex at the depths 1.5 and 3mm; the total dose 1.12±0.3nmol, 9 animals) were performed on pentobarbitone anesthetized spontaneously breathing cats. Amplitudes of abdominal muscle EMG moving averages during mechanically induced tracheobronchial cough decreased by 18% compared to control coughs (p<0.05). The duration between maxima of cough diaphragm and abdominal muscle EMG discharge, cough expiratory phase duration and period of relative motor quiescence between coughs were increased (all p<0.05). Cough number, other cough parameters, and cardiorespiratory characteristics were not altered significantly. Control microinjections of artificial cerebro-spinal fluid had no effect on coughing. Codeine sensitive neurons involved in the generation or modulation of motor pattern of tracheobronchial cough are located in the medullary midline raphé nuclei; however, their contribution to codeine induced cough suppression is limited.