A 54-year-old man complained of burning pain, warm skin and erythema in his extremities. A diagnosis of primary erythromelalgia was made. Microneurography was used to clarify the role of skin sympathetic nerve activity in the pathophysiology of primary erythromelalgia. The patient showed normal skin sympathetic nerve activity but no vasoconstriction response. Aspirin activated the skin sympathetic nerve activity and improved vasoconstriction producing symptomatic relief. These results suggest that the lack of vasoconstriction following vasoconstrictor activity of the skin sympathetic nerves results in increased skin blood flow and burning pain.

Aspirin↗

PubMedDate not supplied

Concentration-dependent variable effects of etoposide on the cell cycle of CML cells.

BACKGROUND: Etoposide, a DNA-topoisomerase II inhibitor, is used for a broad spectrum of cancers with various therapeutic strategies. But the molecular mechanisms of its concentration-dependent effects are not clearly defined. MATERIALS AND METHODS: Chronic myelogenous leukemia K562 cells were treated with low (5 microM) or high (100 microM) concentrations of this drug and the changes of cell cycle progression, expression of cell cycle regulating genes and cyclin B1-dependent histone H1 kinase activity were studied. RESULTS: In the presence of 5 microM etoposide, K562 cells continued to synthesize DNA and most cells showed progress into G2 phase until 24 hours. In contrast, 100 microM etoposide rapidly inhibited DNA synthesis by around 6 hours and most cells remained in their initial phase, while the incorporation of bromodeoxyuridine was partially resumed from 12 hours. The histone H1 kinase activity was only down-regulated in the early phase of 100 microM treated cells. Among the cell cycle controlling genes, c-Myc and P21Cip1/WAF1 showed impressive responses to the two etoposide concentrations. At 100 microM, c-Myc protein rapidly vanished at 3 hours, while p21Cip1/WAF1 was inversely induced from 3 hours. These changes were also observed at 5 microM, but they occurred slowly and weakly. CONCLUSION: The present findings indicate that two concentrations of etoposide functioned as an anticancer agent through modulating the genes related in cell cycle progression. Differing responses of c-Myc and p21Cip1/WAF1 at two concentrations may govern the antiproliferative effects of etoposide.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

MEK and p38MAPK inhibitors potentiate TNF-alpha induced apoptosis in U937 cells.

BACKGROUND: TNF-alpha is one of the key inflammatory cytokines and it modulates various events through several pathways. U937 myelomonocytic leukemia cells are sensitive to TNF-alpha and about 20% of these cells undergo apoptosis within 6 hours after treatment. Co-treatment of these cells with actinomycin D or cycloheximide enhances TNF-alpha induced apoptosis, suggesting that some TNF-alpha-derived signals can augment apoptosis. We investigated whether mitosis-activating protein kinases (MAPKs) had an influence on TNF-alpha induced apoptosis. MATERIALS AND METHODS: U937 cells were treated by TNF-alpha with or without MEK or p38MAPK inhibitors. Apoptosis was assessed morphologically by fluorescence microscopy and caspase-3 was studied by immunoblotting. Expression of apoptosis-inhibitory proteins was studied by RT-PCR whilst the activation of JNKs was investigated by detecting their phosphorylation. RESULTS: TNF-alpha treatment induced apoptosis in about 23% of the cells, while pretreatment with a MEK inhibitor (PD98059) caused 69% of the cells to undergo apoptosis. The inhibition of p38MAPK by SB203580 scarcely enhanced apoptosis, although another p38MAPK inhibitor (PD169316) induced apoptosis in 37% of the cells. Simultaneous pretreatment of cells with PD98059 and PD169316 resulted in the highest level of TNF-alpha induced apoptosis and 90% of the cells underwent apoptosis after 6 hours. In cells pretreated with PD98059 plus PD169316, caspase-3 was completely cleaved at 6 hours and early induction of c-IAP2/HIAP 1 mRNA was not observed. JNKs showed rapid and extensive phosphorylation in these cells. CONCLUSION: TNF-alpha induced apoptosis was potentiated by the inhibition of either MEK alone, or MEK plus p38MAPK, suggesting that the MAPK pathway may be a promising target for cancer therapy.

Apoptosis↗

PubMedDate not supplied

Effect of a centrally-acting muscle relaxant, eperisone hydrochloride, on muscle sympathetic nerve activity in humans.

The sympatho-modulating effects of eperisone hydrochloride, a centrally acting muscle relaxant, on microneurographically recorded muscle sympathetic nerve activity (MSA) were analyzed in human volunteers. A single dose of 300 mg of eperisone was orally administered to 19 healthy subjects aged between 19 and 27, and effects on 1) spontaneous MSA in 30 degrees head-up tilted position, 2) resting MSA and responsiveness to standing, 3) exercise-induced enhancement of MSA were observed. Eperisone has a sympatho-suppressive action in resting skeletal muscles, but has no effect on MSA in actively contracting muscles, e.g. standing, hand-gripping. The sympatho-suppressive effect of eperisone may be related to the drug-induced increase of blood low in the resting skeletal muscles; also it may be one more mechanism through which the drug can exert its muscle relaxant action.

Adult↗

PubMedDate not supplied

Non-Alzheimer non-Pick dementia with Fahr's syndrome.

Five patients with non-Alzheimer non-Pick dementia combined with Fahr's syndrome were studied. Atypical clinical pictures emerged from an evaluation of these cases. Their symptoms and signs could be attributed neither to Alzheimer's disease nor to Pick's disease but to a partial mixture of both. The neuropathological changes were characteristic, and the common findings were as follows: 1) the absence of senile (neuritic) plaques, 2) the widespread presence of numerous neurofibrillary tangles throughout the neocortex, 3) a calcareous deposition of Fahr's type, 4) a circumscribed cerebral atrophy in the temporal or/and frontal lobes, 5) a moderate or severe demyelination and fibrous gliosis in the white matter of the atrophied areas and 6) a mild or moderate neuronal loss in the nucleus basalis of Meynert. These neuropathological changes were not due to Alzheimer's disease nor to Pick's disease. Similar cases reported previously were reviewed.

Aged↗

PubMedDate not supplied

Progressive supranuclear palsy with widespread cerebral lesions.

A 51-year-old woman with no history of any familial neurological diseases initially presented with numbness in her extremities, slowing of movements, comprehension deficit, memory disturbance, dyscalculia, muscle rigidity, hyperreflexia, Parkinsonian gait, increasing disorientation, left-right disturbance, finger agnosia, alexia, acalculia, apraxia, aspontaneity, euphoria, gait disturbance, aphasia, echolalia, and in the terminal stage, mutism, contracture of lower extremities and cachexia. She died of bronchopneumonia at the age of 55. The brain showed widespread cerebral lesions, consisting of nerve cell loss and neurofibrillary tangles in the frontal, parietal and occipital cortex, demyelination and gliosis in the frontal, parietal and occipital subcortical white matter in addition to the typical pathological findings of progressive supranuclear palsy (PSP): severe neuronal loss with gliosis and neurofibrillary tangles (NFTs) in the subthalamic nucleus, globus pallidus and substantia nigra. In conclusion, we present a case of PSP with unusual clinical features (extrapyramidal signs, frontal and parietal lobe syndromes without ophthalmoplegia) and neuropathologically widespread cerebral lesions in addition to the typical pathological findings of PSP. The differential diagnosis of PSP and Alzheimer's disease and other degenerative disorders is discussed.

Alzheimer Disease↗