Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paget's disease of the skull is the main cause of basilar artery syndromes in the adult. They may cause various neurological symptoms, including signs of ischemia of the spinal cord or medulla, or involvement of the cranial nerves and brain stem and, also, distant symptoms due to hydrocephalus, with various mental disorders including transient, recurrent, coma. The authors discuss 30 cases found in the world literature and 6 unreported personal cases, study the clinical symptoms of these cases of basilar artery compression due to Paget's disease, and the methods of neuro-radiological investigation, and emphasize the interest, in severe forms, of early surgical decompression before the stage of severe neurological complications. Regular supervision of patients with Pagets disease is thus essential to detect at an early stage, decompensation of basilar artery insufficiency in Paget's disease. In late forms, calcitonin may be indicated.
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PMID:[Neurologic complications of pagetic basilar impressions and their surgical treatment]. 16 40

Relatively short-term treatment of paraparesis due to Paget's disease with subcutaneous salmon calcitonin alone produced dramatic relief of sensory loss, pain, and paraparesis. The successful outcomes in 2 patients, one with spinal cord and one with cauda equina compression, indicate a potential alternative to surgery in reversing mild-to-severe neural dysfunction in Pagets disease. The proposed mechanisms of action of calcitonin include reduction of a direct bony impingement on the neural tissue and/or a decrease of neural ischemia. It is suggested that even if paraparesis does not improve with calcitonin alone, the medication given preoperatively would probably serve a useful adjunctive role by decreasing intraoperative bone bleeding. However, those patients whose pagetic bone is already metabolically inactive would probably not benefit from calcitonin therapy.
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PMID:Paget's disease. Reversal of severe paraparesis using calcitonin. 47 94

Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome.
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PMID:An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. 221 67

There is now convincing evidence that excessive accumulation of the excitatory amino acid glutamate (Glu) in the extracellular space is toxic to neurons. However, the regulation of the release and uptake of Glu in producing this toxic concentration has not been adequately ascertained. The authors report that in hippocampal slices, the output of Glu significantly increased under in vitro ischemic states. Glu in the extracellular space increased fivefold. Since daurisoline, a drug that blocks N-type Ca2+ channels, or Ca(2+)-free solution potently and effectively lowered this stimulated output, it was hypothesized that the Glu output is mediated by Ca2+ influx in nerve terminals. When the slices were incubated for 30 minutes under ischemic state, daurisoline caused only small alterations in the postischemic accumulation of Glu. However, Glu accumulation was markedly attenuated by H-7, but not by calmidazolium, facilitated by PDB whereas 8-bromo-cAMP was without effect. It appears therefore that during a 30-minute ischemic insult, protein kinase C (PKC) was involved in the Glu accumulation of supernatant. A direct demonstration of this concept was obtained by showing significant increases in PKC activation in presynaptic nerve terminals (from 1.34 +/- 0.1 to 9.34 +/- 0.89 U) following 30 minutes of ischemia. DNQX, a non-NMDA receptor antagonist, potently reduced PKC activities and decreased extra Glu accumulation. Also observed was the inhibition of 1-[3H]-Glu uptake into synaptosomes by PDB. These results provide direct evidence that Ca2+ influx enhances Glu release, which in turn leads to inhibition of its reuptake, and is coupled with PKC activities in presynaptic nerve terminals.
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PMID:Accumulation of glutamate is regulated by calcium and protein kinase C in rat hippocampal slices exposed to ischemic states. 810 81

The presence of the non-selective protein kinase C (PKC) inhibitors, staurosporine (100 nM) and polymyxin B (100 microM) in cultured human RPE cells for more than 24 h triggers apoptotic death. Apoptosis is characterized by a diminishing number of cells, a labelling of nuclei by the TUNEL method and by observable morphological changes. An inhibitor of PKC and cyclic nucleotide-dependent protein kinases, 1-(5-isoquinolinesulphonyl)-2-methyl piperazine (H-7; 100 microM), was without effect, as was the specific PKC inhibitor, calphostin C (100 nM). The PKC-activating phorbol esters, phorbol-12-myristate-13-acetate (PMA; 1 microM) and phorbol-12,13-dibutyrate (PDB; 1 microM) and the non-tumour-promoting phorbol ester, 4 alpha-PMA (1 microM) were without effect, as was the diacyl glycerol analogue, 1,2-dioctanoyl-snglycerol (DOG; 10 microM). The PKC activators did not attenuate the apoptosis induced by staurosporine or polymyxin B. Furthermore, deprivation of glucose and oxygen (simulated ischemia) for 72 h induced apoptosis: this could be prevented by inclusion of 10% (v/v) foetal bovine serum (FBS) but not by a variety of PKC activators. Six PKC isoenzymes were shown to be present in RPE cells (alpha, beta 1, beta 2, delta, epsilon, E) and only the calcium-dependent cPKC levels changed after treatment with staurosporine or simulated ischaemia. Since only the less selective inhibitors of PKC induced apoptosis, it is suggested that PKC is not involved directly in the induction process of apoptosis in RPE cells. It is possible that the staurosporine and polymyxin B-induced effects of apoptosis in RPE cells are triggered by an unknown kinase-dependent pathway, but whether the 'ischaemia'-induced death is related to this same process remains to be elucidated.
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PMID:Induction of apoptosis in cultured human retinal pigmented epithelial cells: the effect of protein kinase C activation and inhibition. 922 Apr 59

Paget's disease of bone (osteitis deformans) is one of the most common skeletal diseases, characterised by bone distortion and the loss of interior structure. Asymptomatic evolution is usual, so diagnosis is likely to be made only when complications of the disease appear. This paper describes such a diagnosis made in a patient with acute lower limb ischemia caused by the compression of the superficial femoral artery between the adductor muscles and an exostosis of the femur.
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PMID:Acute ischemia of the lower limb. An unusual complication of Paget's disease of bone. 1035 Jan 17

Paget's disease of bone is associated with involvement of the central and peripheral nervous system. The brain, spinal cord, cauda equina, spinal roots, and cranial nerves can be affected in Paget's disease due to their anatomic relationship to bone. Neurologic syndromes are uncommon but include headache, dementia, brain stem and cerebellar dysfunction, cranial neuropathies, myelopathy, cauda equina syndrome, and radiculopathies. The central complications result from pagetic involvement of the skull. Expansion of diseased bone can result in compression of cranial nerves as they exit their bony foramina. Softening of the skull leads to basilar invagination with compression of the brain stem, cerebellum, and lower cranial nerves. Brain stem compression can cause hydrocephalus. Rarely, there is direct compression of the brain from acute epidural hematoma or hypertrophy of the calvarium. Myelopathy, cauda equina syndrome, and radiculopathies most commonly result from hypertrophy of the spine with direct compression. Spinal stenosis can also result from ossification of extradural structures or pathologic fractures. Ischemia from vascular compression or a steal syndrome has also been described. Neurologic complications rarely occur due to sarcomatous transformation of pagetic bone. Magnetic resonance imaging (MRI), computerized tomography (CT)-myelography, and bone X-rays are helpful to localize the lesion and direct therapy. Treatment options include surgical decompression, ventricular shunt placement, and medical management with calcitonin and/or the bisphosphonates. The selection of treatment will vary depending upon the rate of progression and the severity of the neurologic deficit.
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PMID:The neurologic complications of Paget's disease. 1051 Feb 21

A review of the literature was conducted to study the pathomechanics by which Paget's Disease of bone (PD) alters the spinal structures that result in distinct spinal pathologic entities such as pagetic spinal arthritis, spinal stenosis, and other pathologies, and to assess the best treatment options and available drugs. The spine is the second most commonly affected site with PD. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12-24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia, when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Since, in the majority of cases with pagetic spinal involvement, there are also coexisting osteoarthritic changes, antipagetic medical treatment alone may be disappointing. Therefore, one must be careful before attributing low back pain to PD alone. Five classes of drugs are available for the treatment of PD: bisphosphonates, calcitonins, mithramycin (plicamycin), gallium nitrate, and ipriflavone. Bisphosphonates are the most popular, and several forms have been investigated, but only the following forms have been approved for clinical use: disodium etidronate, clodronate, aledronate, risedronate, neridronate, pamidronate, tiludronate, ibadronate, aminohydroxylbutylidene bisphosphonate, olpadronate, and zoledronate. Several of these forms are still under investigation.
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PMID:Paget's disease of the spine and its management. 1171 91

Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms. Recently, an increasing number of medical reports have implicated osteoporotic fractures as a cause of serious neurological deficit and painful disabling spinal deformities. This has been corroborated by the present authors as well. These complications are only amenable to surgical management, requiring instrumentation. Instrumenting an osteoporotic spine, although a challenging task, can be accomplished if certain guidelines for surgical techniques are respected. Neurological deficits respond equally well to an anterior or posterior decompression, provided this is coupled with multisegmental fixation of the construct. With the steady increase in the elderly population, it is anticipated that the spine surgeon will face serious complications of osteoporotic spines more frequently. With regard to surgery, however, excellent correction of deformities can be achieved, by combining anterior and posterior approaches. Paget's disease of bone (PD) is a non-hormonal osteometabolic disorder and the spine is the second most commonly affected site. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12-24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients, back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. In this context, one must be certain before attributing low back pain to PD exclusively, and antipagetic medical treatment alone may be ineffective. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Five classes of drugs are available for the treatment of PD. Bisphosphonates are the most popular antipagetic drug and several forms have been investigated.
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PMID:Principles of management of osteometabolic disorders affecting the aging spine. 1450 19

Human placental decidua basalis-mesenchymal stem cells (PDB-MSCs) are multipotent cells from the human term placenta, which are ethically conducive, easily accessible and high-yielding source. PDB-MSCs can differentiate into adipogenic, osteogenic and neurogenic cells under appropriate conditions, which may be an attractive and alternative source of seed cells for tissue engineering. To investigate the effect of hypoxia (1% O2) on human PDB-MSCs and the expression of cytokine, PDB-MSCs were isolated from human placenta by density gradient centrifugation and cultured in the Dulbecco's modified Eagle's medium-high glucose (DMEM-HG) containing 10% fetal bovine serum (FBS), and the fifth passage of PDB-MSCs were taken. PDB-MSCs were divided into 4 groups according to the concentrations of O2 and FBS: 20% O2, 10% FBS; 20% O2, 0% FBS; 1% O2, 10% FBS; 1% O2, 0% FBS. The proliferation and apoptosis of PDB-MSCs were detected by MTT and flow cytometric analysis at the time points of 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h, respectively. Vascular endothelial growth factor (VEGF) released from PDB-MSCs was detected by enzyme-linked immunosorbent assay (ELISA) at the same time points. The results showed that hypoxia enhanced the proliferation of PDB-MSCs at 12 h under the condition of 10% FBS, while at 24 h under the condition of 0% FBS (P<0.01, n=3). In normoxia, the cells cultured in 10% FBS displayed a significant proliferation compared to those cultured in 0% FBS. However, in hypoxia, the number of cells cultured in 0% FBS (serum deprivation) increased significantly compared to that cultured in 10% FBS at 24 h and 96 h respectively (P<0.05, P<0.01, n=3). With the flow cytometric analysis of cell apoptosis under the condition of hypoxia and serum deprivation, we found that hypoxia and serum deprivation did not induce PDB-MSCs apoptosis (P>0.05, n=3). This conclusion may relate to the expression of VEGF which needs further research. In conclusion, the results obtained indicate that PDB-MSCs are able to bear hypoxia and serum deprivation, suggesting that PDB-MSCs can be used as seed cells for ischemia related tissue engineering.
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PMID:[Effects of hypoxia on human placental decidua basalis-mesenchymal stem cells proliferation, apoptosis and VEGF expression.]. 1908 35


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