Biomedical subjects

F Block

Publications and source records attributed to F Block.

At least 55 records · Page 3Linked to original sources

PubMed2000

[Immobilization hypercalcemia as a complication of polyneuropathy].

Prolonged immobilization or physical inactivity has been shown to produce increased bone resorption due to enhanced osteoclastic activity and diminished bone formation. These skeletal changes are a typical complication in tetraplegic patients, who are at risk of developing hypocalcemia. Hypercalciuria is the most characteristic symptom. However, some patients develop hypercalcemia, which is infrequent in these patients, and the hypercalcemia can become a life-threatening complication. Until now, it has been unclear why a small percentage of immobilized patients develop hypercalcemia. Here we present a case of symptomatic hypercalcemia (serum calcium: 3.5 mM/l) following immobilization due to a critical illness polyneuropathy. The diagnosis could be established after malignant hypercalcemia, primary hyperparathyroidism, and other causes of hypercalcemia were excluded. Treatment with intravenous saline, furosemide, and calcitonin was not effective in lowering serum calcium. Treatment with pamidronate (Aredia) was successful and reduced the serum calcium to normal values.

Anti-Inflammatory Agents↗

PubMed2000

[Clinico-neurologic aspects of acute inflammatory brain diseases].

Despite the progress, which has been made in diagnosis and therapy of encephalitis and bacterial meningitis, these acute inflammatory diseases of the brain still display a certain amount of morbidity and mortality. History, physical examination, analysis of serum and cerebrospinal fluid and radiological examination are the mainstay for the diagnosis of these diseases. With respect to the acute inflammatory diseases of the brain computed tomography and magnetic resonance imaging fulfill three purposes: 1. They can be used to clarify the diagnosis and to rule out other diseases. 2. They can identify the focus from which a bacterial meningitis can evolve. 3. Complications like edema, cerebral vasculitis, septic sinus thrombosis, hydrocephalus or abscess can be visualized. If the diagnosis is made early, the possible complications are recognized in good time and the appropriate therapy is started immediately, then morbidity and mortality can be kept at a minimum.

Brain↗

PubMed2000

[Isolated vasculitis of the central nervous system].

Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid.

Biopsy↗

PubMed2000

Presumed capillary telangiectasia of the pons: MRI and follow-up.

Capillary telangiectasia is a vascular abnormality primarily of the brainstem. The clinical relevance is unclear as is the association with clearly pathologic findings such as cavernous haemangioma. We report on four cases with capillary telangiectasia proven by follow-up and describe the imaging characteristics. T2 abnormality was only observed in half of the patients as was the presence of a discernable collecting vein. Whereas two cases were incidental findings in neurologically normal persons and one had symptoms clearly attributable to lacunar stroke, one patient may have had symptoms due to the vascular abnormality in the pons.

Adult↗

PubMed1999

[Neuroprotection in stroke. A critical overview].

Cerebral ischemia leads to a cascade of pathophysiological processes which contribute to ischemic cell damage. In addition to the excitotoxicity, which is characterized by a massively elevated extracellular concentration of excitatory amino acids and an intracellular overload with calcium, the increased formation of free radicals, the inflammation and the apoptosis are also involved in ischemic damage. Neuroprotection, a pharmacological interaction with these pathophysiological processes, is one possibility to attenuate the consequences of cerebral ischemia. In experimental studies it could be demonstrated that glutamate antagonists, calcium antagonists or radical scavengers reduce the ischemic damage. Substances which interact with inflammation or apoptosis have also been shown to be protective. Clinical trials, however, showed no beneficial effects. This discrepancy is mainly due to differences in the design of the studies. In experimental studies the substances were often applied before or at the onset of ischemia, the survival time after ischemia was very short and the effects of neuroprotection were mainly evaluated by morphological examinations. Considering these points in future preclinical studies it is hoped that neuroprotective substances will be found which may be effective in clinical trials.

Animals↗

PubMed1999

[Neurologic diseases and pregnancy].

Neurological diseases during and following pregnancy represent a small subgroup of all neurological diseases. They can be divided into three groups. 1) Diseases which existed already before pregnancy or which appear just by chance during this phase like migraine, multiple sclerosis, myasthenia gravis, epilepsy, brain tumors or Guillain-Barre syndrome. 2) Diseases that can appear without pregnancy but which display a higher incidence in connection with pregnancy. Cerebral ischemia, intracerebral hemorrhage, subarachnoidal hemorrhage, intracranial venous thrombosis and compression neuropathies belong to this group. 3) Preeclampsia/eclampsia, HELLP syndrome, amniotic fluid embolism and pituitary apoplexy are diseases with neurological symptoms which occur only with pregnancy. The pregnancy itself can imply some restrictions or even a contraindication concerning diagnosis and therapy of these diseases. The decision in favour or against diagnostic or therapeutic approaches is determined by possible effects on the fetus and by potential danger resulting from not recognizing or not treating such a disease.

Diagnosis, Differential↗

PubMed1999

Global ischemia and behavioural deficits.

Global cerebral ischemia in rodents is an established model in experimental research on cerebral ischemia which is characterized morphologically by a selective neuronal damage in the hippocampus, striatum and cortex. Using this model many studies have been performed to examine the pathophysiology of ischemic neuronal damage. Based upon these results it has been analysed whether substances which interact with the pathophysiological processes reduce the ischemic neuronal damage. Besides the morphological changes global ischemia leads to functional changes which can be assessed by behavioural studies. The Morris water maze examines the animals' abilities to learn, remember and go to a place in space only defined by its position relative to distal extramaze cues. In this test ischemic animals display a deficit in spatial learning as revealed by an increase in latency and in swim distance in the escape trials and a deficit in spatial memory as shown by reduced quadrant time and crossings over the former platform position during the probe trial. In several studies it could be demonstrated that neuroprotective strategies which reduce ischemic neuronal damage also attenuate or even completely prevent the ischemia-induced behavioural deficits in the water maze. Transplantation of fetal tissue which can also be used to achieve morphological recovery following global ischemia results in an amelioration of the ischemia-induced deficit. Thus, the water maze can clearly show that transplanted tissue can be functionally relevant. Data from the water maze seem to be a valuable completion to morphology which is especially important with respect to the relevance of experimental studies for clinical trials.

Animals↗

PubMed1998

Expression of interleukin 6 in the rat striatum following stereotaxic injection of quinolinic acid.

Stereotaxic intrastriatal injection of the naturally occurring N-methyl-D-aspartate (NMDA) agonist quinolinic acid (QA) serves as a valuable in vivo model to study excitotoxic cell damage in the central nervous system (CNS). Although morphological changes such as neuronal loss, glial activation and remote reactions following QA injection have been described in some detail, much less is known about the molecular mechanisms mediating the accompanying glial response. Cytokines are known to play a crucial role in almost all kinds of CNS alterations. We now demonstrate that IL-6, a multifunctional glycoprotein which belongs to the family of neurokines, is expressed endogenously in the rat striatum following QA injection. Using Northern blot analysis, a massive but transient upregulation of IL-6 mRNA could be detected. This started 3 h after QA injection, reached a maximum at 6 h and disappeared within 24 h. That activated microglia are the most likely cellular source of the observed corresponding IL-6 protein expression could be concluded by comparing the immunocytochemical pattern of IL-6 expression and microglial activation. Interestingly, astrocytes initially downregulate their expression of glial fibrillary acidic protein (GFAP) in the excitotoxically injured striatum, but show a delayed increase in GFAP immunoreactivity starting in the periphery of the striatum, subsequently expanding to the core. The early transient IL-6 expression may play an important role in initiating the delayed astrocytic response following excitotoxic cell injury.

Animals↗

PubMed1998

Flupirtine, a nonopioid centrally acting analgesic, acts as an NMDA antagonist.

1. Flupirtine (Katadolon) is a member of a class of triaminopyridines and is used as a nonopioid analgesic agent with muscle relaxant properties. 2. In situ experiments have revealed that flupirtine protects against ischemic-induced insults to the retina and brain. 3. Data derived from in vitro and in vivo studies suggest that flupirtine functions as a weak N-methyl-D-aspartate (NMDA) antagonist with little evidence that it acts on AMPA-kainate type glutamate receptors. 4. No evidence could be found from binding studies to suggest that flupirtine has an affinity for any of the characterized binding sites associated with the NMDA receptor. 5. Studies on cultured cortical neurons show that the NMDA-induced influx of 45Ca2+ is more readily decreased by flupirtine when a reducing agent (dithiothreitol) is present. However, when N'-ethylmaleimide, which is thought to alkylate the NMDA receptor redox site, is present, no obvious effect on the NMDA-induced influx of 45Ca2+ is produced by flupirtine. 6. Flupirtine is also known to counteract the production of reactive oxygen species caused by ascorbate/iron as well as to prevent apoptosis in cells lacking NMDA receptors induced by oxidative stress. 7. To explain all the experimental data, it is suggested that flupirtine affects the redox state/pH/electrons in the cell. The specific way by which flupirtine antagonizes the NMDA receptor might be by an action on the known redox site of the receptor.

Aminopyridines↗

PubMed1998

The b-wave of the electroretinogram as an index of retinal ischemia.

1. The b-wave of the electroretinogram (ERG) is a particularly sensitive index of retinal ischemia. The present paper summarizes the changes in the b-wave observed in five in vivo models of retinal ischemia. 2. Although the amount of reduction in b-wave amplitude during ischemia corresponds to the severity of the insult, the degree of recovery of the b-wave during reperfusion depends on the duration of ischemia. 3. A massive release of glutamate, intracellular overload with calcium and enhanced production of free radicals are suggested to be three major pathophysiological processes that contribute to retinal ischemic damage. The b-wave of the ERG represents a functional measure for potential therapeutic efficacy of drugs interacting with these pathophysiological processes. 4. Several glutamate antagonists, such as MK-801, memantine, flupirtine or GYKI 52466, along with the free radical scavengers vitamin E, lipoate, superoxide dismutase and catalase, all reduce the depression of the b-wave during ischemia or accelerate the recovery of the b-wave during reperfusion or both. The calcium channel antagonists nimodipine and levemopamil exert only a slight beneficial effect on the recovery of the amplitude of the b-wave during reperfusion, provided that the blood pressure is not potently reduced.

Animals↗

PubMed1998

Global ischemic neuronal damage relates to behavioural deficits: a pharmacological approach.

Global cerebral ischemia leads morphologically to selective neuronal damage in the CA1 sector of the hippocampus and in the striatum and functionally to a deficit in spatial learning and memory in the water maze. The results of earlier studies which examined the relationship between neuronal damage and the deficits in the water maze were not clear cut. It has been observed, however, that neuroprotection reduces both the deficits in the water maze as well as the neuronal damage. The present study therefore approached the relationship between the neuronal damage and the deficits in water maze using pharmacological means. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 min. Ischemic rats were treated with the N-methyl-D-aspartate receptor antagonist dextromethorphan, 50 mg/kg, with the calcium antagonist levemopamil, 30 mg/kg, with the radical scavenger EPC-K1, 10 mg/kg, or with solvent. Treatment with dextromethorphan or levemopamil reduced the deficit in spatial learning by limiting the increase in swim distance due to ischemia. Both substances also reduced the deficit in spatial memory by minimizing the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial. EPC-K1 had no influence on the ischemia-induced behavioural changes. Group comparisons demonstrated that the swim speed and the percentage of the swimming path along the sidewall were affected neither by ischemia nor by any of the treatments. Histological examination revealed neuronal damage in the hippocampus and in the striatum in all of the ischemic rats. Treatment with dextromethorphan or levemopamil reduced the hippocampal damage by 32% and 36%, respectively. In addition, dextromethorphan diminished the striatal damage about 78%. Correlation analysis demonstrated a correlation between the cumulative swim distance of all 20 escape trials and hippocampal damage (r = 0.65, P < 0.001) but not between swim distance and striatal damage (r = 0.14, P = 0.364). No correlation was found between quadrant time of the probe trial and either hippocampal damage (r = -0.21, P = 0.19) or striatal damage (r = -0.02, P = 0.889). The average percentage of the swimming path along the side wall related to the hippocampal damage (r = 0.28, P = 0.035) but not to the striatal damage (r = 0.05, P = 0.381). With respect to the average swim speed a correlation to striatal damage was observed (r = -0.69, P < 0.001) but not to hippocampal damage (r = -0.15, P = 0.168). These results clearly demonstrate that using the pharmacological approach it is possible to uncover certain correlations between functional deficits in the water maze and neuronal damage which are both due to global cerebral ischemia.

Animals↗

PubMed1997

Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats.

In this study the effect of post-treatment with rolipram, an inhibitor of cAMP phosphodiesterase, on neuronal damage following global ischemia was evaluated. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 minutes. Rolipram was administered 6 hours after onset of ischemia and thereafter the following 7 days daily once at a dose of 0.3 or 3.0 mg/kg intraperitoneally. Four weeks after ischemia the amount of intact neurons in the hippocampus and in the striatum was assessed following perfusion fixation. The ischemia-induced neuronal damage in the CA1 sector of the hippocampus and in the striatum was reduced by rolipram at either dose. The present results show that treatment with rolipram reduces ischemic neuronal damage at a therapeutic window of 6 hours.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Retinal ischemia induced by the intraluminal suture method in rats.

In a model of transient focal cerebral ischemia in male Sprague-Dawley rats, which is induced by the intraluminal suture method, the acute effects on the electrical function of the retina were monitored by recording the electroretinogram. The electroretinogram was recorded from halothane-anesthetized rats before, during and after vascular occlusion through the intraluminal suture method for 180 min. During vascular occlusion the amplitude of the a- and b-wave were markedly suppressed. Upon reperfusion the a-wave recovered immediately. During reperfusion up to 48 h the amplitude of the b-wave increased to approximately 50% of the pre-occlusion value did not fully recover. Immunohistochemistry of the retinas revealed that the vascular occlusion induced the expression of glial fibrillary acidic protein in retinal Müller cells. The present data suggest that the intraluminal suture method leads to retinal ischemia.

Animals↗

PubMed1997

Flupirtine reduces functional deficits and neuronal damage after global ischemia in rats.

Global cerebral ischemia leads to selective neuronal damage in the CA1 sector of the hippocampus and in the dorsolateral striatum. In addition, it results in deficits in spatial learning and memory as shown by an increase in escape latency and swim distance during the escape trials and a reduction of time spent in the quadrant of the former platform position during the probe trial of the water maze. Flupirtine is a non-opioid, centrally acting analgesic which has been shown to be neuroprotective against N-methyl-D-aspartate (NMDA)-mediated toxicity in vitro. The purpose of the present study was to investigate the potential protective effect of flupirtine in vivo with both behavioural and histological measures of global cerebral ischemia. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Flupirtine was administered at a dose of 5 mg/kg i.p. either 20 min before and 50 min after occlusion (pre-treatment) or directly and 70 min after occlusion (post-treatment). 1 week after surgery, spatial learning and memory was tested in the Morris water maze. Pre-treatment with flupirtine reduced the increase in escape latency and in swim distance induced by 4VO. It also diminished the deficit in spatial memory as revealed by an increase in time spent in the quadrant of the former platform position during the probe trial which was reduced by 4VO. Post-treatment with flupirtine had no effect on the deficits in spatial learning and memory induced by 4VO. Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated with pre-treatment of flupirtine whereas post-treatment did not affect this neuronal damage. The present data demonstrate that pre-treatment with flupirtine exerts a protective effect on hippocampal and striatal neuronal damage and on deficits in spatial learning induced by 4VO.

Aminopyridines↗

PubMed1997

Effects of antioxidants on ischemic retinal dysfunction.

Transient occlusion of both common carotid arteries in normotensive rats leads to a reduction in the amplitude of the b-wave of the electroretinogram (ERG). The present study investigated whether the antioxidants vitamin E and lipoate attenuate the depression and enhance the recovery of the b-wave of the ERG in response to retinal ischemia. The ERG was recorded from halothane-anesthetized rats before. during and after transient (24 min) occlusion of both common carotid arteries. The substances were administered 20 minutes before or at the onset of ischemia. Both vitamin E (100 mg kg-1) and lipoate (100 mg kg-1) significantly reduced the depression of the b-wave during occlusion and accelerated recovery during reperfusion at either time point of application. The present results suggest that antioxidants provide protection against ischemic retinal dysfunction.

Animals↗

PubMed1997

Carotid artery dissections presenting as isolated posterior cerebral artery infarctions.

A spontaneous dissection of the carotid artery is a well-known cause of cerebral infarction, mostly due to an embolus from the affected vessel segment. For haemodynamic and anatomical reasons the territories of the middle and anterior cerebral arteries are usually involved. We report two cases of carotid artery dissections resulting in infarctions exclusively in the territory of the posterior cerebral artery. The underlying anatomical conditions were a fetal origin of the posterior cerebral artery and an embolic supra-ophthalmic occlusion of the internal carotid artery. To our knowledge similar cases have not previously been documented.

Aortic Dissection↗

PubMed1997

Correlation between hippocampal neuronal damage and spatial learning deficit due to global ischemia.

Global cerebral ischemia leads to selective neuronal damage in the CA1 sector of the hippocampus and in the striatum. This ischemia leads to a deficit in spatial learning and memory in the water maze. The results of earlier studies that have examined the relationship between neuronal damage and the deficit in the water maze were not clear-cut. It has been observed that neuroprotection reduces both the deficit in the water maze and the neuronal damage. The present study therefore approached the relationship between the neuronal damage and the deficit in the water maze by pharmacological means. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 min. Ischemic rats were then treated with the noncompetitive non-NMDA receptor antagonist GYKI 52466 (30 mg/kg), the radical scavenger LY 231617 (20 mg/kg), the inhibitor of protein kinase C staurosporine (0.1 mg/kg), or solvent. Treatment with GYKI 52466 or LY 231617 reduced the deficit in spatial learning by limiting the increase in swim distance due to ischemia. In addition, LY 231617 reduced the deficit in spatial memory as demonstrated by minimizing the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial. Staurosporine had no influence on the ischemia-induced behavioural changes. Histological examination revealed neuronal damage in the hippocampus and in the striatum in all of the ischemic rats. However, treatment with GYKI 52466 or LY 231617 reduced the hippocampal damage. Correlation analysis demonstrated a correlation between hippocampal damage and total swim distance (r = 0.88, P < 0.001). No correlation was found between hippocampal damage and quadrant time of the probe trial (r = -0.24, p > 0.1). No correlation was observed between striatal damage and either total swim distance of the escape trials (r = 0.28. p > 0.1) or quadrant time of the probe trial (r = -0.08, p > 0.6). It is concluded that a correlation exists between hippocampal damage and the deficit in spatial learning following global cerebral ischemia.

Animals↗

PubMed1996

Dextromethorphan reduces functional deficits and neuronal damage after global ischemia in rats.

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a transient locomotor hyperactivity and a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of dextromethorphan, an antagonist at the N-methyl-D-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. Dextromethorphan was administered 20 min before induction of ischemia at a dose of 10 or 50 mg/kg. Before and on day 1, 3 and 5 after operation the spontaneous locomotor activity was measured. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damage was assessed. Treatment with 50 mg/kg of dextromethorphan reduced the increase in locomotor activity observed on day 1 and 3 after ischemia. In the water maze dextromethorphan reduced the increase in escape latency and in swim distance induced by 4VO. Furthermore, the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial was increased by treatment with dextromethorphan. Neuronal damage in the CA1 sector of the hippocampus and in the dorsolateral striatum produced by 4VO was significantly attenuated by dextromethorphan. The present results demonstrate that protective effects on neuronal damage may be related to an attenuation of deficits in spatial leaning and memory following global ischemia.

Animals↗