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Biomedical subjects

A Fabian

Publications and source records attributed to A Fabian.

At least 19 recordsLinked to original sources

A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration.

Cell migration relies on a tight temporal and spatial regulation of the intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i in turn depends on Ca2+ influx via channels in the plasma membrane whose molecular nature is still largely unknown for migrating cells. A mechanosensitive component of the Ca2+ influx pathway was suggested. We show here that the capsaicin-sensitive transient receptor potential channel TRPV1, that plays an important role in pain transduction, is one of the Ca2+ influx channels involved in cell migration. Activating TRPV1 channels with capsaicin leads to an acceleration of human hepatoblastoma (HepG2) cells pretreated with hepatocyte growth factor (HGF). The speed rises by up to 50% and the displacement is doubled. Patch clamp experiments revealed the presence of capsaicin and resiniferatoxin (RTX)-sensitive currents. In contrast, HepG2 cells kept in the absence of HGF are not accelerated by capsaicin and express no capsaicin- or RTX-sensitive current. The TRPV1 antagonist capsazepine prevents the stimulation of migration and inhibits capsaicin-sensitive currents. Finally, we compared the contribution of capsaicin-sensitive TRPV1 channels to cell migration with that of mechanosensitive TRPV4 channels that are also expressed in HepG2 cells. A specific TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate, does not increase the displacement. In summary, we assigned a novel role to capsaicin-sensitive TRPV1 channels. They are important Ca2+ influx channels required for cell migration.

Calcium↗

[Psychosocial factors and depressive disorders: pathogenesis model and intervention strategies].

This article gives an overview of the impact of psychosocial factors on the manifestation and course of depressive disorders. It focusses primarily on the large body of work done by G.W. Brown and his co-workers since the 1970s on the pathogenesis of depression. A systematic approach to the treatment of depression should contain not only specific psychotherapy as well as antidepressant drug treatment, but should also include interventions of a psychosocial nature. There are so far hardly any controlled studies in this area. So-called "befriending" projects and psychosocial support schemes for at-risk groups, e.g. single mothers, promise to be interesting approaches. Befriending in this context means a specific kind of relationship that differs structurally from the relationship between a therapist and his client. Interventions of this type on the basis of the prevalence of depressive disorders could have a substantial impact on public health.

Depressive Disorder↗

Guillain-Barre syndrome in patient with Burkitt's lymphoma and type 2 diabetes mellitus.

Although peripheral neuropathies are commonly observed in patients with non-Hodgkin's malignant lymphomas (NHML), Guillain-Barre syndrome (GBS) belongs to the occasional complications of lymphoproliferative disorders. It appears in less than 0.3 per cent of NHML. It is worthy of note that in the reported case there occurred three independent risk factors of peripheral neuropathy: Burkitt's lymphoma, chemotherapy and type 2 diabetes mellitus. Based on clinical course, EMG finding and neuropathological examination, in spite of normal cerebrospinal fluid protein content, GBS as a paraneoplastic disorder was diagnosed. It was assumed that chemotherapy and diabetes mellitus conduced to severe neuropathy.

Burkitt Lymphoma↗

Vascular factors are critical in selective neuronal loss in an animal model of impaired oxidative metabolism.

Thiamine deficiency (TD) models the cellular and molecular mechanisms by which chronic oxidative deficits lead to death of select neurons in brain. Region- and cell-specific oxidative stress and vascular changes accompany the TD-induced neurodegeneration. The current studies analyzed the role of oxidative stress in initiating these events by testing the role of intercellular adhesion molecule-1 (ICAM-1) and endothelial nitric oxide synthase (eNOS) in the selective neuronal loss that begins in the submedial thalamic nucleus of mice. Oxidative stress to microvessels is known to induce eNOS and ICAM-1. TD increased ICAM-1 immunoreactivity in microvessels within the submedial nucleus and adjacent regions 1 day prior to the onset of neuronal loss. On subsequent days, the pattern of ICAM-1 induction overlapped that of neuronal loss, and of induction of the oxidative stress marker heme oxygenase-1 (HO-1). The intensity and extent of ICAM-1 and HO-1 induction progressively spread in parallel with the neuronal death in the thalamus. Targeted disruption of ICAM-1 or eNOS gene, but not the neuronal NOS gene, attenuated the TD-induced neurodegeneration and HO-1 induction. TD induced ICAM-1 in eNOS knockout mice, but did not induce eNOS in mice lacking ICAM-1. These results demonstrate that in TD, an ICAM-1-dependent pathway of eNOS induction leads to oxidative stress-mediated death of metabolically compromised neurons. Thus, TD provides a useful model to help elucidate the role of ICAM-1 and eNOS in the selective neuronal death in diseases in which oxidative stress is implicated.

Animals↗

[Evaluation of nervous system disorders during the course of gastric carcinoma on the basis of clinical electrophysiologic analysis].

The complex of neurological symptoms, which occur in the course of neoplasms of the internal organs and caused by the distant effect of the neoplasm on the nervous system, excluding other factors which could be responsible for changes in the nervous system, is called the paraneoplastic syndrome (PS). Pathogenesis of PS has not been clearly explained so far. Besides toxic, metabolic and infectious causes, the autoimmunologic one is taken into consideration. Paraneoplastic syndrome is mostly evoked by the oat cell carcinoma, subsequently by the breast, ovary and rarely by gastric carcinoma. The aim of the work was to determine: 1) the changes in the electroneurographic as well as visual and auditory evoked potentials examinations in the course of gastric carcinomas, 2) the influence of the treatment applied in gastric carcinomas on changes in visual and auditory evoked potentials and electroneurographic examinations. The examined group included 33 patients with diagnosed gastric carcinoma and having no clinical symptoms of lesion of the central and peripheral nervous systems. The results were compared to the control group, which consisted of healthy volunteers and patients after ventricular resection because of the chronic peptic ulcer disease. Clinical, neurographic as well as visual and auditory evoked potentials examinations were carried out three times. I.--just after the diagnosis of the neoplastic disease, II.--after end of treatment, III.--after 18 months (on average) since the end of the therapy. All patients had operative treatment. A part of them had supplementary chemotherapy--EEP cycle (Etoposide, Epirubicin, Cisplatin) or 5-fluorouracil. On the basis of the performed examinations of patients with gastric carcinoma, without clinical symptoms of lesions of the nervous system, primary axonal sensory-motoric neuropathic changes were observed in 36%. Changes in visual and auditory evoked potentials were found only in patients over 65 years old in over 50%. In patients after chemotherapy they were observed in visual and auditory evoked potentials and electroneurographic examinations, which could be caused by neurotoxic side-effect of the cytostatics applied.

Adult↗

Subacute cerebellar degeneration as a remote effect of breast cancer.

Clinical investigations on the case of a 61-year-old woman with a few year history of neurological symptoms, who underwent mastectomy caused by ductal carcinoma, 12 years prior to the appearance of the clinical syndrome did not reveal the cause of the disease. On the post-mortem examination solitary metastasis of adenocarcinoma to the retroperitoneal lymph node was present. Histologically, in the cerebellum the degeneration of the Purkinje cells with extensive Bergmann glia reaction was diagnosed. The authors discuss the connection between lesions of CNS and neoplastic disease.

Breast Neoplasms↗

Impaired EDRF production by endothelial cells exposed to fibrin monomer and FDP.

Fibrin and fibrinogen and their proteolytic degradation products, found within the atheroma, may contribute to vascular dysfunction. We monitored the production of endothelium-derived relaxing factor (EDRF) by bovine aortic endothelial cells (BAEC) after exposure to fibrinogen, fibrin monomer (FM), and fibrin and fibrinogen degradation products (FDP). Cells incubated with FM and FDP, compared with cells incubated with fibrinogen, were less able to inhibit platelet aggregation, and this effect correlated with a concentration-dependent decrease in EDRF production: BAEC incubated with FM or FDP, but not fibrinogen, produced significantly less nitric oxide (NO), as determined using a photolysis-chemiluminescence system. Northern analysis of BAEC incubated with fibrinogen, FM, or FDP and probed for constitutive bovine endothelial NO synthase mRNA demonstrated decreased expression in cells exposed to FDP or FM. These data show that FM and FDP reduce EDRF produced by BAEC and attenuate constitutive NO synthase expression. These effects may represent a mechanism by which thrombotic determinants adversely affect endothelial function and thereby potentially impair vasomotor responses and contribute to atherothrombogenesis.

Amino Acid Oxidoreductases↗

Cavernous angioma of brain stem mimicking multiple sclerosis.

A 14-year-old boy was admitted to our Department due to peripheral palsy of right VII and bilateral of the VI cranial nerves, spasticity, cerebellar symptoms as well as to dysphagia and dysarthria. In general, he was hospitalized 13 times because of the disease of a relapsing-remitting and next progressive course. He died 31 years after onset of the disease. Multiple sclerosis was diagnosed. Brain autopsy revealed tumor involving almost all brain stem structures and a part of right cerebellar hemisphere. Histologically, cavernous angioma was diagnosed.

Adolescent↗

Pitfalls in computed tomography of the cervical and lumbar spine.

In 10 patients, evaluated by computed tomography studies of the spine, radiological findings alone may have led to misinterpretation of the clinical condition. Five patients demonstrated CT findings of cervical disc herniation or protrusion, while clinical examination resulted in the diagnosis of neuralgic amyotrophy. In contrast, 3 patients with clinical signs of compression of lumbar nerve roots had negative findings in CT studies of the lumbar discs. Additional slices at the level of the vertebral body, however, demonstrated free sequestration of disc substance. Two patients with signs of compression of cervical roots had normal CT findings, but extensive disc herniation was present at surgery.

Aged↗

Multiple disseminated meningioma. Case report.

A case of 32-year-old woman was described in which progressive bilateral hearing and visual loss, hypokinesia, epileptic focal seizures were present. The brain CT-scan after a few years of the disease onset, showed the presence of multiple extracerebral tumors. Multiple meningiomas were diagnosed, probably associated with von Recklinghausen's disease. On the post-mortem examination 48 tumors of the different size and location in subdural space were found. Histologically transitional meningiomas with predominance of fibroblastic component were diagnosed. It was very interesting that apart from intracranial location of meningiomas, the same type of tumor was found within thoracic spinal root. The authors discuss the mechanisms of the development of multiple meningiomas and its association with neurofibromatosis.

Adult↗

[Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-- a prospective study].

Using a quantitative standardized procedure, the swelling of the ankle produced by supination trauma was measured. In the 66 patients with fresh rupture of the lateral ligament treated surgically at our Department between December 1986 and April 1987, a prospective study of the effect of serrapeptase (Aniflazym) on post-operative swelling and pain was carried out in 3 randomized groups of patients. In the group receiving the test substance, the swelling had decreased by 50% on the third post-operative day, while in the other two control groups (elevation of the leg, bed rest, with and without the application of ice) no reduction in swelling had occurred at that time. The difference is statistically significant (p = 0.013). Decreasing pain correlated for the most part with the reduction in swelling. Thus, the patients receiving the test substance more rapidly became pain-free than did the control groups. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with the classical conservative measures, for example, the application of ice.

Adult↗

[Course of conservatively treated acute lumbar root compression syndrome. A computer tomography controlled study].

Of 129 patients with an acute lumbar root compression syndrome due to disc herniation 21, who were symptom-free, were examined by computed tomography (CT) on average 276 days after a three-step regimen of conservative treatment. In no instance had there been a deterioration of the original findings. In 14 patients the CT picture continued to demonstrate disc herniation, although the patients were without symptoms. In two patients a moderate, in five a marked regression of herniation was demonstrated by CT. Clinical improvement without change in the CT picture points to the compression syndrome not being explainable solely in mechanical terms. As a matter of fact, a possible cause may be a disturbance of radicular blood supply resulting in oedematous root swelling which is usually masked in the CT by prolapsed disc tissue. There is as yet no easy explanation for regression in case of prolapsed, perhaps even sequestered, disc tissue. It is possible that there have been reparative processes, such as have been described histopathologically in form of ingrown vessels. More plausibly would be a separation of the herniated and/or sequestered disc tissue in form of an asymptomatic sliding into the terminal caudal region.

Adult↗

Central antiarrhythmic effects of imidazole in anesthetized rats.

In urethane anesthetized rats, the intracerebroventricular (icv.) microinjection of sodium glutamate or KCl induced cardiac arrhythmias. These cardiac rhythm disorders could be prevented by the icv. administration of imidazole. The i.v. injection of the same doses of imidazole elicited cardiac arrhythmias. The antiarrhythmic activity of imidazole is probably due to its ability to stimulate phosphodiesterase activity, which leads to a decrease in cGMP and/or cAMP cerebral levels.

Anesthesia↗

Central antiarrhythmic activity of adenosine in anesthetized rats.

In urethane-anesthetized rats the intracerebroventricular (icv.) administration of sodium glutamate or desipramine induced cardiac arrhythmias. These cardiac rhythm disturbances could be prevented by icv. administration of adenosine. The i.v. injection of adenosine had an arrhythmogenic action. The antiarrhythmic effect of adenosine could be reversed by icv. aminophylline. It is suggested that the antiarrhythmic activity of adenosine is due to the central inhibition of release of acetylcholine, and/or noradrenalin, produced by the decreased availability of calcium for the excitation-secretion coupling.

Adenosine↗

[Changes in the length of sleep cycles during administration of flurazepam and lopirazepam].

The influence of narcotics on the duration of the ultradian NREM/REM cycle can be clearly recognized only when the first, particularly instable cycle is also included in the evaluation. A study with Lopirazepame and Flurazepame showed that compared to placebo Lopirazepame prolonged the first cycle particularly. In contrast with Flurazepame the first, but mainly the second cycle was shortened, and not until the third NREM/REM cycle the duration was compatible with that of placebo and Lopirazepame. The result is, that in nights of the same length Flurazepame shows a half or one cycle more compared to Lopirazepame.

Adolescent↗

The influence of oxytocin on the fibrillation thresholds in rabbits.

The intravenous infusion of oxytocin in urethane anaesthetized rabbits induced marked increases of both atrial and ventricular fibrillation threshold. The heart rate and the arterial blood pressure (BP) diminished. Since there was no parallelism between the fibrillation threshold changes and those of heart rate and BP, it might be concluded that the changes of the fibrillation thresholds were very likely primary, i.e. they were due to the modifications of the electrophysiological properties of the heart. The intravenous infusion of 0.5% chlorbutol , a preservant widely used in many commercial preparations induced only minor changes of the investigated parameters.

Animals↗