[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.

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.

[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.

[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.

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.

Calcium antagonists as a peripherally acting labyrinthine suppressant in humans.

A total of 908 patients with peripheral vestibular disorders were treated with calcium antagonists for periods of 10 to 120 days in a series of controlled clinical trials using a placebo or other medication for comparison. The cumulative analysis of the results indicates that cinnarizine, flunarizine and bencyclan have produced good clinical results, particularly in patients with vascular problems. A comparison between different doses used in different trials revealed a correlation of good clinical results to smaller doses of some of these medications.

[Treatment of disorders of cerebral performance in the aged in ambulatory care using bencyclane. Results of a controlled double-blind phase III study versus placebo]. / Die Behandlung von Hirnleistungsstörungen im Alter in der ambulanten Praxis mit Bencyclan. Ergebnisse einer kontrollierten Doppelblindstudie Phase III versus Placebo.

A placebo-controlled, randomized double-blind study conducted at a general practitioner's surgery was designed to investigate the efficacy of bencyclane in 120 outpatients with cerebral dysfunctions based on organic brain syndrome. The study started with a 4-week placebo washout phase and then continued with a 12-week treatment phase. 200 mg Bencyclane-hydrogenfumarate was administered b.i.d. Efficacy was assessed by a doctor's symptom rating (SCAG) and a study nurse's rating (BGP) as well as by two performance tests (CFF and ZVT-G). Data from 106 patients (52 under bencyclane and 54 under placebo) were statistically analysed. More side effects were seen under bencyclane than under placebo, in particular insomnia, headache, akathisia, nausea and vomiting. As an a priori hypothesis, it was stated that after alpha-adjustment there should be a statistically significant difference in symptomatology (SCAG, BGP) and performance (CFF, ZVT-G). With regard to performance, the zero hypothesis could be rejected on the 5% level, and on the 1% level with respect to symptomatology. The experimental error on both the performance and the symptom level was below 6%. The drug effects were significant on a confirmatory level and are considered to be also of clinical relevance.

[Hemodynamic disorders and various problems in treatment in strokes with reversible neurologic deficits]. / Narusheniia gemodinamiki i nekotorye voprosy lecheniia pri insul'te s obratimym nevrologicheskim defitsitom.

The authors studied the parameters of the systemic and cerebral circulation in 58 patients with a stroke involving a reversible neurological deficit and compared them with the clinical course of the disease and analogous parameters in 53 patients with ischemic stroke. The efficacy of some vasoactive drugs in a combined treatment of "minor stroke" was evaluated.

Effects of bencyclane on concussion following head injury in mice.

Bencyclane showed a dose-dependent anti-concussive effect with a duration of at least 60 minutes in an experimental model of concussion induced by head injury. This long-lasting effect cannot be explained only by the changes in the serum level of the agent or the increase in brain circulation due to its vasodilative action, both of which are of much shorter durations. Our findings suggest that bencyclane causes alterations in brain metabolism, which is partly responsible for reduction in the duration of the experimental concussion.

[Demonstration of bencyclane effects in a clinico-pharmacologic vigilance model]. / Darstellungen von Bencyclanwirkungen in einem klinisch-pharmakologischen Vigilanzmodell.

The effects of 8 weeks' treatment with 2x 200 mg Bencyclan daily were investigated versus placebo in 50 patients. A clinical diagnosis had revealed the onset of organic mental disorders in all patients who, after fulfilling neurophysiologically and neuropsychologically defined screening criteria, were admitted to the trial. The patients were randomly allocated to two parallel groups of 25 for this controlled, double-blind study. Patients had to show 50% subvigil phases in a 15 min resting-EEG recording. We define such behaviour as a neurophysiological disturbance of vigilance. Scores in the Benton test were to be 2 points below the expected value or the NAF-score was to be above a standard value attained in an old people's home (greater than 14). On a neurophysiological level, inference statistical tests indicated effects in line with the hypothesis: A statistically significant difference in favour of Bencyclan was apparent after 8 weeks' treatment when compared with placebo. The Vigilance Index (VI) was higher under Bencyclan than after placebo. We regard the VI as a plausible indicator of vigilance-dependent disturbances in the elderly. On a behavioral level, Bencyclan was tendentially superior with respect to age-dependent complaints and performance-related activatedness, whereby one could not exclude the possibility that there were chance findings. The clear proof of efficacy on the neurophysiological level and the unclear effectiveness on the behavioral level can be attributed to the fact that time- and placebo effects were less marked on the former level. The intensive supervision of the patients led to considerable placebo effects on the behavioral level. Two groups of 25 patients are therefore not sufficient to be able to detect drug effects within a treatment period of only 8 weeks.