[The neuroprotective therapy of outpatient treatment of chronic cerebral ischemia].

AIM: To perform a differential analysis of the efficacy of combination therapy by the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I- III. MATERIAL AND METHODS: A study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I - 20 patients, stage II - 20, stage III - 10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with a 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course. RESULTS AND CONCLUSION: The therapeutic efficacy after durable complex therapy by repeated courses of antioxidants is supported by the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. To increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients.

Broadband near-infrared emission in Tm3+-Dy3+ codoped amorphous chalcohalide films fabricated by pulsed laser deposition.

Structural and near-infrared (NIR) emission properties were investigated in the Tm(3+)-Dy(3+) codoped Ge-Ga-based amorphous chalcohalide films fabricated by pulsed laser deposition. The homogeneous films illustrated similar random network to the glass target according to the measurements of X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy. An 808 nm laser diode pumping generated a superbroadband NIR emission ranging from 1050 to 1570 nm and the other intense broadband NIR emission centered at ~1800 nm, which was attributed to the efficient energy transfer from Tm(3+) to Dy(3+) ions. This was further verified by the broad-range excitation measurements near the Urbach optical-absorption edge involved defect states. The results shed light on the potential highly integrated planar optical device applications of the codoped amorphous chalcohalide films.

Effect of bencyclane fumarate on intestinal ischaemia reperfusion injury.

BACKGROUND: Post-ischaemic intestinal tissue damage appears to be due to the formation of oxygen radicals. Free radical-initiated lipid peroxidation following intestinal ischaemia/reperfusion (I/R) may disrupt mucosal integrity. Indirectly, the radicals trigger the accumulation of neutrophils within the affected tissue, initiating inflammatory processes that lead to severe mucosal lesions. We have investigated the protective effect of bencyclane fumarate, a vasodilating Ca(2+) channel blocker, which has been used for the treatment of peripheral arterial occlusive diseases, on intestinal ischaemia reperfusion (IR) injury in rats. METHODS: Forty-eight Wistar albino rats were divided into three groups: a sham-operated group (no IR injury, n = 16), an ischaemic control group (IR, n = 16), and BF-treated group (pretreatment 5 mg/kg bencyclane fumarate + IR, n = 16). A marker for lipid peroxidation, namely malondialdehyde; free radical scavengers, glutathione peroxidase, catalase and superoxide dismutase levels; an index of polymorphonuclear neutrophils, myeloperoxidase activity and mucosal damage were investigated. RESULTS: Malondialdehyde levels, myeloperoxidase activity and the severity of mucosal damage were decreased in the BF group. In addition, in the BF group, glutathione peroxidase, catalase and superoxide dismutase levels were higher compared with the IR group. CONCLUSION: The pretreatment of rats with bencyclane fumarate before intestinal ischaemia attenuates the mucosal damage in intestinal IR injury, probably by altering lipid peroxidation, neutrophil accumulation and antioxidant activity.

[Patogenetic therapy of patients with diabetes mellitus type 2 and cerebral vascular insufficiency].

Effectiveness of halidor preparation was assessed in a randomized open 8-weeks study in 44 patients with diabetes mellitus type 2 and chronic cerebral blood circulation disorders. A control group included 15 patients with the same pathologies who did not receive halidor. Administration of halidor in doses 100 mg 3 times daily led to the improvement of clinical state in 32 (72,7%) patients that was confirmed by statistically better performance (p<0,05) on the neuropsychological tests: MMSE by 14,7%, clock-drawing test by 16,8%, the Schult test by 23,5%. The blood flow in middle and posterior cerebral arteries was increased by 21 and 23%, respectively (p<0,05), and the vascular tonus was reduced. The possibility of halidor administration to patients with diabetes mellitus with concomitant chronic cerebral blood circulation disorders is discussed.

[Halidor in the treatment of cerebral vascular diseases in emergency cases].

An aim of the study was to assess efficacy and safety of an injection form of galidor (bencyclan) in patients with chronic cerebral vascular diseases in cases of emergency. Sixty patients with discirculatory encephalopathy (DE), including 38 with basilar insufficiency, were treated. Mean age of patients was 59,7 years. Halidor was injected slowly intravenous in dosage 50 mg (13 patients) or 100 mg (56 patients) during 5 minutes. After treatment, the following symptoms were observed: sluggishness (2,8% of patients), excitement (0,9%), hyperhydrosis (0,9%), coordination disturbance (0,9%). Halidor does not cause side-effects and complications in 90% of patients. The results obtained suggest high efficacy of galidor in DE. A good effect has been achieved in 72,5% of cases, fair effect in 20,3%, no effect has been found in 7,2%.

[Metabolic effects of mexidol in complex treatment of chronic brain ischemia].

Patients with a chronic brain ischemia of stages I-II on the background of hypertension and/or cerebral atherosclerosis are characterized by energy insufficiency of the metabolism, as estimated by the activity of succinate dehydrogenase in peripheral blood lymphocytes. Within the framework of randomized comparative investigation of the efficiency of actovegin and mexidol in the complex therapy of a chronic brain ischemia, positive dynamics in reduction of the clinical semiology, restoration of cognitive processes in the brain, and reduction of the expression of subjective manifestations of the disease is established. On this background, the administration of mexidol led to restoration of the energy exchange due to substrate effects of the Krebs cycle intermediates present in its structure.

[Severe bencyctane intoxication--a case report]. / Ciezkie zatrucie bencyklanem--opis przypadku.

Bencyclane relaxes smooth muscles of vasculature and has been used in the treatment of peripheral and cerebral circulation disorders. Bencyclane penetrates the blood brain barrier and may evoke various adverse central effects, such as psychotic episodes, coma, and convulsions. It also decreases arterial pressure by vasodilatation and has negative inotropic action. The cardiodepressive action of bencyclane is caused probably by a direct calcium-channel antagonistic mechanism. The case of a 23-year old man, addict on amphetamine, who ingested 5 g of bencyclane (Halidor) is presented. The patient developed coma, convulsions, shock and cardiogenic pulmonary edema. He required mechanical ventilation, treatment with pressure amines (dopamine and dobutamine) and calcium. The circulatory and respiratory insufficiency persisted to the seventh day of hospitalization, then the patient was completely recovered and confirmed suicidal ingestion of 50 tablets a 100 mg of Halidor. In cases of severe bencyclane intoxications most important is an intensive symptomatic treatment. In these cases extracorporeal methods of toxin elimination from the blood are probably completely inutile, because of large bencyclane volume of distribution.

[An experience with the clinical use of halidor in the treatment of chronic lower limb ischemia]. / Opyt klinicheskogo ispol'zovaniia galidora v lechenii khronicheskoi ishemiei nizhnikh konechnostei.

The paper is concerned with a study into the effect of halidor on the results of conservative (17cases) and surgical (22 cases) treatment of patients suffering from chronic lower limb ischemia. The surgical treatment included revascularization interventions. The study groups were compared to the respective control groups of patients who did not receive halidor. As compared to the control group, the group undergoing surgical treatment demonstrated a significant increase in the ankle/brachial index after parenteral infusion of halidor administered in courses (p<0.05). Also, in the group undergoing conservative treatment, there was a significant increase in the distance of painless walking.

Bencyclane as an anti-sickling agent.

A vasodilating Ca2+ channel blocker, bencyclane, was used in 18 patients with homozygous sickle cell anaemia (SCD) to test the possible anti-sickling effect. With bencyclane intervention the Na(+)-K+ ATPase activity increased from 256 +/- 29 to 331 +/- 37 nmol Pi/mg protein/h (P < 0.0001) and the Ca(2+)-Mg2+ ATPase level increased from 172 +/- 12 to 222 +/- 44 nmol Pi/mg protein/h (P < 0.0001). The intracytoplasmic Ca2+ concentration reduced from 3.5 +/- 0.6 to 2.7 +/- 0.25 mumol/l (P < 0.0001). The patient's blood contained fewer irreversibly sickled cells (ISCs) (a reduction from 21.4% to 14.4%) (P < 0.05). At the same time MCHC of the erythrocytes decreased from 34.5 to 33.0 g/dl (P < 0.05). Bencyclane appears to be a promising anti-sickling agent that can be used orally in SCD.

Walk training and drug treatment in patients with peripheral arterial occlusive disease stage II. A review.

On the basis of the present studies physical therapy is the most effective basis therapy of peripheral arterial occlusive disease stage II according to Fontaine. The consequent integration of the patients into widespread vascular training groups would be desirable. All present studies with so-called vasoactive drugs led to a statistically significant increase in pain-free walking distance. This is especially true for the substances naftidrofuryl, pentoxifylline, and buflomedil. Nevertheless, these studies do not fully meet the standards set by the GCP or the FDA guidelines. It must also be said that the increase in walking distance by vasoactive substances is less pronounced than the effect obtained by walk training alone. Both the vasoactive therapy and controlled walk training aim at an increase in pain-free walking distance. It is, however, still unclear whether the modes of therapy described influence the primary disease. Angiographically controlled studies are momentarily not available.

Influence of deproteinized hemodialysate on rest pain and walking distance in the presence of peripheral chronic arterial occlusive disease.

In a controlled and randomized single-blind study (blind observer) the clinical efficacy of intra-arterial therapy with a metabolically active deproteinized dialysate from calf blood has been tested against a vasodilating and hemorheologically active reference substance (bencyclan). Over a period of four weeks 28 patients each received 20 intra-arterial infusions of the deproteinized hemodialysate 20% for infusion. The reference group with 30 patients was treated with 250 mg bencyclan in 250 mL saline 0.9%. As for the target criteria, rest pain and consumption of analgesics, the hemodialysate treatment proved superior to the therapy with the reference substance. Both preparations induced to a small extent pain-free walking distances: hemodialysate group, 29.2 +/- 14.6 m; reference group, 25.8 +/- 18.7 m (group difference not significant).

Determination of bencyclane in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of bencyclane in human plasma is presented. Bencyclane was extracted from human plasma with two 3-ml volumes of isooctane and was shaken for 10 min. The organic phase was separated and evaporated to dryness at 40 degrees C under a nitrogen stream. The residue was dissolved and an aliquot was injected into the gas chromatograph. The separation was performed with a DB-17 column with helium as the carrier gas. Nitrogen-selective detection was performed. The quantification was performed with the signal output. The limit of detection was 1 ng/ml.

The long-term tolerability of bencyclane ('Fludilat') in patients with peripheral occlusive disease: a 48-week prospective double-blind controlled study versus placebo.

In a controlled, multi-centre, double-blind trial, 75 patients with Stage II peripheral occlusive disease (Fontaine IIa) were treated with either 200 mg bencyclane twice daily or placebo over a period of 12 months. Undesired drug effects and concomitant phenomena were documented, and efficacy was evaluated. Bencyclane caused a slight, clinically negligible decrease in blood pressure. The pulse rate remained mostly unchanged, ECG and laboratory parameters showed no changes which would indicate a specific effect of the test substance. In the context of the generally low incidence of concomitant effects, patients in the bencyclane group mentioned symptoms such as insomnia, depressive mood, sweating and reduced motoricity more often than those in the placebo group. These symptoms are regarded as signs of the central nervous actions of the drug. The parameters used to assess the efficacy, i.e. the pain-free walking distance estimated by the patients and the physician's global judgment based on Ratschow's test, the palpability of the pedal pulse, the walking range and the patients' subjective statements about the incidence of chill, formication, and pain in the legs, showed a constant and statistically significant superiority of bencyclane over placebo.

[Bencyclane in stage II arterial occlusive disease. Results of a controlled study]. / Bencyclan bei arterieller Verschlusskrankheit im Stadium II. Ergebnisse einer kontrollierten Studie.

In a single-center, double-blind, randomized study, 19 patients with peripheral arterial occlusive disease stage II Fontaine were treated with bencyclan, and a further 19 patients with buflomedil for 10 weeks after a wash-out phase of 2 weeks. Both groups showed a significant increase in painfree and total walking distances. No significant difference was found between the two groups.

Effects of bencyclane on normal and cevadine-modified Na channels in frog skeletal muscle.

The effect of 10(-5) mol/l bencyclane on the repetitive electrical activity of muscle membrane was studied with the conventional microelectrode technique. Electrical activity was induced by repetitive stimulation in normal Ringer solution (train) or by a single depolarizing current pulse in the presence of 10(-6) mol/l cevadine (volley). Bencyclane decreased, in a use-dependent manner, the maximum rates of depolarization and repolarization (Vmax+ and Vmax-, resp.) of the action potentials both of the train and the volley. The inhibition of Vmax+ and Vmax- was proportional; however, it was stronger for the volleys than for the trains. The cycle length (mean interspike interval) of the volley was increased by bencyclane; the prolongation was progressive during consecutive cycles. The dissociation of bencyclane from the Na channel was studied by applying trains of different durations with equal pulse numbers. Bencyclane at a higher concentration (5 x 10(-5) mol/l) caused a reversible tonic block: the overshoot potentials, Vmax+ and Vmax- were markedly reduced. The reduction of Vmax- was slightly stronger than that of Vmax+. Slow membrane potential oscillation (SMPO) was evoked by treating the muscle with 10(-4) mol/l of cevadine. The administration of 5 x 10(-6) mol/l bencyclane decreased the frequency of SMPO, while 10(-5) mol/l bencyclane terminated the slow oscillation activity without changing its baseline potential. The present results indicate that bencyclane induces use-dependent inhibition of Na channels in muscle, similarly as do class 1 antiarrhytnmic drugs. Inhibition was observed with both normal and cevadine-modified Na channels.

Slow channel inhibitor effects on brain function: tolerance to severe hypoxia in the rat.

1. The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. 2. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and 'background-EEG'. Drugs were administered i.v. 5 min before the onset of hypoxia. 3. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. 4. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear-cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. 5. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect.